AR101 Trial in Europe Measuring Oral Immunotherapy Success in Peanut Allergic Children (ARTEMIS)
Phase: PHASE3
Conditions: Peanut Allergy
Sponsor: Aimmune Therapeutics, Inc.

 
 
 
CLINICAL STUDY PROTOCOL 
 
 
 
 
ARC010 
AR101 Trial in Europe Measuring Oral Immunotherapy Success in 
Peanut Allergic Children (ARTEMIS) 
 
 
 
 
Protocol Version 4.0, Amendment 3.0 – 28 Aug 2018 
Reference Numbers:  NCT03201003, EudraCT 2016-005004-26 
 
 
 
 
 
 
 
 
 
 
 
Aimmune Therapeutics, Inc. 
8000 Marina Blvd, Suite 300 
Brisbane, CA  94005 
United States 
 
 
 

CLINICAL STUDY PROTOCOL 
Protocol Title: 
AR101 Trial in Europe Measuring Oral 
Immunotherapy Success in Peanut Allergic Children 
(ARTEMIS) 
Study Phase: 
Phase 3 
Investigational Drug 
AR101 
Protocol Number: 
ARC010 
IND Number: 
15463 
EudraCT Number: 
2016-005004-26 
Sponsor: 
Aimmune Therapeutics, Inc.  
8000 Marina Blvd, Suite 300 
Brisbane, CA 94005 
United States 
 
Version 
Date 
1.0 (Original) 
23 December 2016 
2.0 (Amendment 1.0) 
16 January 2017 
2.1 (Country-specific Amendment – Germany) 
24 May 2017 
2.2 (Country-specific Amendment – Sweden) 
21 Jun 2017  
(not implemented) 
2.3 (Country-specific Amendment – Sweden) 
20 July 2017 
2.4 (Site-Specific Amendment – Imperial College 
Healthcare NHS Trust, UK) 
21 July 2017 
3.0 (Amendment 2.0) 
26 September 2017 
3.1 (Site-Specific Amendment – Imperial College 
Healthcare NHS Trust, UK) 
20 October 2017 
4.0 (Amendment 3.0) 
28 August 2018 
 
This study will be conducted according to the Declaration of Helsinki (2013), principles of Good Clinical 
Practice as described in International Council for Harmonisation guidelines, including the archiving of 
essential documents, EU Directive 2001/20/EC (the Clinical Trials Regulation), EU Directive 2005/28/EC 
(Good Clinical Practice Directive), and local applicable legislation including but not limited to the UK SI 
2004/1031 Medicines for Human Use (Clinical Trials) Regulations 2004 as amended. 
Confidentiality Statement 
This document is confidential and is to be distributed for review only to investigators, potential investigators, 
consultants, study staff and applicable independent ethics committees or institutional review boards.  The 
contents of this document shall not be disclosed to others without prior written authorization from Aimmune 
Therapeutics, Inc., unless it is necessary to obtain informed consent from potential study subjects. 
 

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CLINICAL STUDY PROTOCOL ARC010 
Sponsor Personnel 
 
Clinical Lead, 
Clinical Operations: 
Sharon Vadher 
Aimmune Therapeutics 
 
Chief Medical 
Officer: 
Daniel C. Adelman, MD 
Aimmune Therapeutics  
 
 
Medical Monitor: 
Stuart McIntosh, BM BS, MRCS, MD, FFPM 
Aimmune Therapeutics 
 

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Principal Investigator Protocol Approval 
 
 
 
 
 
Protocol ARC010 
Protocol 4.0 (Amend 3.0) 
Date:  28 Aug 2018 
IND: 15463 
EudraCT: 2016-005004-26 
 
Short Title: ARTEMIS 
 
I have read this clinical study protocol.  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, and according to the criteria 
specified in this protocol.  Furthermore, I will conduct this protocol in keeping with local, 
national, and international requirements.   
 
_______________________________                   
Principal Investigator (Print) 
 
 
 
_______________________________ 
 
_______________ 
Principal Investigator (Signature) 
 
 
Date 

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Protocol ARC010 Synopsis 
Title 
AR101 TRIAL IN EUROPE MEASURING ORAL IMMUNOTHERAPY SUCCESS IN 
PEANUT ALLERGIC CHILDREN (ARTEMIS) 
Short Title 
ARTEMIS  
Clinical Phase 
3 
IND 
15463 
EudraCT 
2016-005004-26 
IND Sponsor 
Aimmune Therapeutics, Inc. 
Number of Subjects 
Approximately 160 peanut-allergic subjects will be randomized 3:1 to AR101 
peanut oral immunotherapy (OIT) versus placebo.  
Objectives 
The primary objective is to demonstrate the efficacy of AR101, a pharmaceutical-
grade peanut allergen formulation, through reduction in clinical reactivity to 
limited amounts of peanut allergen in peanut-allergic children and adolescents 
(ages 4 to 17 years, inclusive). 
The secondary objectives are: 
• 
To demonstrate the safety of AR101 as measured by the incidence of 
adverse events (AEs), including serious adverse events (SAEs). 
• 
To evaluate the immunological effects of peanut OIT therapy. 
Study Design 
This is a European, multicentre, 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 will consist of a Screening 
phase that includes a Screening double-blind, placebo-controlled food challenge 
(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.  
Eligible subjects will receive escalating doses of either AR101 or placebo. 
Eligible subjects who reach the targeted dose of 300 mg/d and maintain that dose 
for approximately 12 weeks will undergo an Exit DBPCFC; subjects may have a 
dose reduction because of an AE but must be on a dose of 300 mg/d without 
symptomatic therapy for the 4 weeks immediately preceding the Exit DBPCFC. 
Subjects who do not reach the maintenance dose of 300 mg/d will be discontinued 
from the study. 
An Exit 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 12 weeks). Each subject will be unblinded when he/she 
completes the Exit DBPCFC at the end of the approximately 12-week 
Maintenance Period, all major data queries (ie, queries that could influence 
allocation to 1 or another analysis population) for the subject have been resolved, 
and the follow-on study ARC008 is available at the study site.  
All placebo-treated subjects who complete ARC010 are eligible for rollover into 
the follow-on study ARC008. In the follow-on study, placebo-treated subjects 
from ARC010 will undergo an initial escalation and up-dosing schedule identical 
to that for subjects who received AR101 in ARC010.  
All AR101-treated subjects in ARC010 who tolerate the single challenge dose of 
300 mg peanut protein (443 mg cumulative) during the Exit DBPCFC are eligible 
to proceed to the follow-on study. Subjects who complete 12 weeks of 
maintenance and experience dose-limiting symptoms (DLS) at the exit challenge 
at the dose of 300 mg peanut protein (443 mg cumulative) or below will not be 
eligible to enroll in ARC008.  
If ARC008 is not yet available at the study site, subjects may continue blinded 
study treatment and have clinic visits every 4 weeks in ARC010 until ARC008 is 

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Protocol ARC010 Synopsis 
Title 
AR101 TRIAL IN EUROPE MEASURING ORAL IMMUNOTHERAPY SUCCESS IN 
PEANUT ALLERGIC CHILDREN (ARTEMIS) 
available. Subjects who do not tolerate 300 mg peanut protein at the Exit 
DBPCFC will not continue blinded study treatment in ARC010.  
The end of the study is defined as the last visit of the last subject.  
A Data Safety Monitoring Committee (DSMC) will be established to monitor the 
study for safety.  
Study Duration 
Each subject will participate in the study for up to approximately 14 months.  
The expected duration of the study is approximately 18 months. 
Primary Endpoint 
The primary clinical efficacy endpoint is the proportion of subjects who tolerate 
at least 1000 mg as a single dose (2043 mg cumulative) of peanut protein with no 
more than mild symptoms at the Exit DBPCFC. 
Secondary Efficacy 
Endpoints 
Key Secondary Efficacy Endpoints 
• 
The proportion of subjects who tolerate at least 600 mg as a single dose 
(1043 mg cumulative) of peanut protein with no more than mild 
symptoms at the Exit DBPCFC  
• 
The proportion of subjects who tolerate at least 300 mg as a single dose 
(443 mg cumulative) of peanut protein with no more than mild 
symptoms at the Exit DBPCFC 
• 
The maximum severity of symptoms occurring following ingestion of 
peanut protein during the Exit DBPCFC 
Other Secondary Efficacy Endpoints 
• 
Maximum tolerated dose (MTD) with no more than mild symptoms at 
Exit DBPCFC 
• 
Change from baseline in MTD of peanut protein at Exit DBPCFC 
• 
Use of epinephrine as a rescue medication at Exit DBPCFC and 
comparison to its use at Screening DBPCFC 
• 
Changes in serum peanut- and peanut component-specific IgE, total IgE, 
and peanut-specific IgG4 levels 
• 
Changes in peanut skin prick test (SPT) mean wheal diameter 
• 
Quality of life assessment using the food allergy quality of life 
questionnaire (FAQLQ), and the food allergy independent measure 
(FAIM) questionnaire 
Exploratory Endpoints 
• 
Treatment satisfaction assessment using the Treatment Satisfaction 
Questionnaire for Medication (TSQM-9) and an Exit Questionnaire. 
• 
Assessment of palatability (taste and after-taste) 
Safety Endpoints 
• 
The safety of peanut OIT based on AEs and SAEs 
• 
Use of epinephrine as a rescue medication during OIT (Initial Escalation, 
Up-dosing, and Maintenance Periods) 
• 
Frequency and severity of anaphylaxis during OIT (Initial Escalation, 
Up-dosing, and Maintenance Periods), attributable to investigational 
product (IP) or accidental food exposure 
• 
Frequency and severity of allergic reaction (hypersensitivity) AEs 
occurring during the Up-dosing versus the Maintenance Period, 
normalized for duration of treatment 

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Protocol ARC010 Synopsis 
Title 
AR101 TRIAL IN EUROPE MEASURING ORAL IMMUNOTHERAPY SUCCESS IN 
PEANUT ALLERGIC CHILDREN (ARTEMIS) 
• 
Frequency of accidental ingestion of peanut and other allergenic foods; 
frequency and severity of reactions resulting from accidental ingestion of 
peanut and other allergenic foods 
• 
Frequency and severity of premature discontinuation of dosing due to 
AEs; and frequency of premature discontinuation of dosing due to 
chronic/recurrent gastrointestinal (GI) AEs 
• 
Assessment of asthma control using the 2007 National Heart, Lung, and 
Blood Institute (NHLBI) classification and the Asthma Control Test 
questionnaire in subjects with asthma 
Investigational 
Product and 
Dispensing 
AR101 or placebo. Doses characterized and normalized for total protein and 
specific peanut allergen ratios will ascend per the dosing regimen in the Initial 
Escalation Period Dosing Schedule and Up-dosing Period Dosing Schedule at the 
end of the synopsis. 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. Capsules for 
dose escalation and up-dosing will be supplied in blister packs. For the 
Maintenance Period, 300 mg of peanut protein will be supplied in foil-laminate 
sachets. Matching placebo sachets will be used to maintain the blind. Trained 
investigational site personnel will dispense the IP to the subject’s parent or 
guardian in a manner consistent with the assigned dose level. IP will be dispensed 
in a double-blinded fashion according to subject randomization number, using a 
proprietary interactive response system.  
Inclusion Criteria 
• 
Age 4 through 17 years (inclusive) 
• 
Clinical history of allergy to peanuts or peanut-containing foods 
• 
Serum IgE to peanut ≥ 0.35 kUA/L, inclusive (as determined by 
UniCAP™ within the past 12 months) and/or a peanut SPT wheal 
diameter ≥ 3 mm compared to control 
• 
Experience DLS at or before the 300 mg (444 mg cumulative) challenge 
dose of peanut protein (measured as 600 mg of peanut flour) on 
Screening DBPCFC conducted in accordance with PRACTALL 
(Practical Issues in Allergology, Joint United States/European Union 
Initiative) guidelines 
• 
Written informed consent from subject or parent/guardian for all subjects 
(or both parents when required by local authorities) 
• 
Written assent from minor subjects as appropriate (in accordance with 
local regulatory requirements) 
• 
Use of effective birth control by female subjects of childbearing 
potential (Section 7.10.3.2) 
Exclusion Criteria 
• 
History of hemodynamically significant cardiovascular disease, 
including uncontrolled or inadequately controlled hypertension 
(Section 5.10) 
• 
History of severe or life-threatening episode of anaphylaxis or 
anaphylactic shock within 60 days of Screening DBPCFC 
• 
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 including autoimmune 
diseases and malignancies (including malignancies occurring in the 5 
years prior to Screening) 

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Protocol ARC010 Synopsis 
Title 
AR101 TRIAL IN EUROPE MEASURING ORAL IMMUNOTHERAPY SUCCESS IN 
PEANUT ALLERGIC CHILDREN (ARTEMIS) 
• 
History of eosinophilic esophagitis (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 
• 
Current participation in any other interventional study and/or 
participation in another interventional clinical study within 30 days or 5 
half-lives of the IP, whichever is longer, prior to randomization 
• 
Participation in, and having received active treatment in, any previous 
clinical study of AR101 CODIT™ 
• 
Currently receiving, or having received in the 5 years prior to Screening, 
any type of peanut or any other food immunotherapy (including 
subcutaneous, sublingual, oral, or epicutaneous)  
• 
Subject is in “build-up phase” of immunotherapy to another allergen (ie, 
has not reached maintenance dosing) 
• 
Severe asthma (2007 NHLBI Criteria Steps 5 or 6, Appendix 2) 
• 
Mild or moderate asthma (2007 NHLBI Criteria Steps 1-4), if 
uncontrolled or difficult to control as defined by any of the following: 
o 
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 
o 
Inhaled corticosteroid (ICS) dosing of > 500 mcg daily fluticasone 
(or equivalent ICS based on NHLBI dosing chart); or 
o 
1 hospitalization in the past year prior to Screening for asthma; or  
o 
Emergency room (ER) visit for asthma within 6 months prior to 
Screening 
• 
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:  
o 
history of daily corticosteroid dosing for > 1 month during the past 
year; or 
o 
1 corticosteroid course in the past 3 months; or  
o 
> 2 corticosteroid courses in the past year ≥ 1 week in duration  
• 
Inability to discontinue antihistamines 5 half-lives before the initial day 
of escalation, SPT, or Screening DBPCFC 
• 
Lack of an available palatable vehicle food to which the subject is not 
allergic 
• 
Use of any therapeutic antibody (eg, omalizumab, mepolizumab, 
reslizumab, dupilumab, etc.) or any other immunomodulatory therapy 
excluding aeroallergen or venom immunotherapy, or corticosteroids 
within the past 6 months (Section 5.10) 
• 
Use of beta blockers (oral), angiotensin-converting enzyme (ACE) 
inhibitors, angiotensin-receptor blockers (ARB), calcium channel 
blockers, or tricyclic antidepressants (Section 5.10) 
• 
Pregnancy or lactation 
• 
Residing at the same address as another subject in this or any peanut OIT 
study 
• 
Developing DLS(s) in reaction to the placebo part of the Screening 
DBPCFC 

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Protocol ARC010 Synopsis 
Title 
AR101 TRIAL IN EUROPE MEASURING ORAL IMMUNOTHERAPY SUCCESS IN 
PEANUT ALLERGIC CHILDREN (ARTEMIS) 
• 
History of a mast cell disorder, including mastocytosis, urticaria 
pigmentosa, and hereditary or idiopathic angioedema, and chronic 
spontaneous urticaria or other physician-diagnosed physical urticaria 
syndrome 
• 
Allergy to oat 
• 
Hypersensitivity to epinephrine or any of the excipients in the IP 
• 
Any other condition that, in the opinion of the investigator, precludes 
participation for reasons of safety 
• 
Inability to follow the protocol requirements 
• 
Patients being in any relationship or dependency with the sponsor and/or 
investigator 
• 
Subjects with a history of alcohol, medication or drug abuse 
Treatment Description 
Screening/baseline: Eligible subjects will undergo a DBPCFC at the end of the 
Screening portion of the study. The Screening DBPCFC will be an abbreviated 
version of the DBPCFC described in the PRACTALL guidelines, progressing 
only up to a top challenge dose of 300 mg (444 mg cumulative) of peanut protein 
or placebo. Additionally, the DBPCFC will progress through the dose levels in a 
fixed sequence, without repeating any dose. Those subjects who have DLS at or 
before the 300 mg (444 mg cumulative) challenge dose of peanut protein 
(measured as 600 mg of peanut flour) will be randomized 3:1 to active treatment 
(AR101) or placebo.  
For each subject, a Blinded Evaluating Physician is to be designated to assess the 
tolerability of the challenge doses presented in the DBPCFC. The Blinded 
Evaluating Physician (or Blinded Assessor) is not to be involved directly in the 
oversight of study product dosing or the assessment or management of AEs 
during the initial escalation, up-dosing, or maintenance phases of the study; nor 
should they be involved in the food challenge material preparation on the food 
challenge days. To the extent practicable, the same Blinded Evaluating Physician 
who determines DLS in the Screening DBPCFC should determine DLS in the 
Exit DBPCFC. 
Initial Escalation (2 consecutive days): Eligible subjects will be randomized and 
initiate OIT 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 at least a 3 mg dose will be 
considered escalation failures and will be discontinued from the study. Subjects 
who tolerate both the 3 mg and 6 mg doses of IP, or who tolerate the 3 mg but not 
the 6 mg dose, will undergo confirmatory testing of the tolerability of a 3 mg dose 
the following consecutive day (refer to Initial Escalation Schedule at end of 
synopsis). Subjects who tolerate this confirmatory dose will enter the Up-dosing 
Period. Subjects who do not tolerate this confirmatory dose will be discontinued. 
Therapy details are found in Section 3 and Section 6 of the protocol. 
Up-dosing: Subjects will receive daily oral dosing of peanut or placebo OIT for 
approximately 20 weeks, if up-dosing proceeds without holding at, or reducing, a 
dose level; up to 40 weeks, maximum. All escalation doses will be administered 
in a 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 capability requirements for 
monitoring and emergency intervention are met by the facility). All up-dosing 
activities will be performed under direct observation. Therapy details are found in 
Section 3 and Section 6 of the protocol.  

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Protocol ARC010 Synopsis 
Title 
AR101 TRIAL IN EUROPE MEASURING ORAL IMMUNOTHERAPY SUCCESS IN 
PEANUT ALLERGIC CHILDREN (ARTEMIS) 
Maintenance: Those subjects who reach the target maintenance dose of 300 mg/d 
of IP will enter an approximately 12-week Maintenance Period of continued 
dosing at 300 mg/d weeks, which may be extended by up to an additional 4 weeks 
(for a maximum Maintenance Period duration of 16 weeks), or to a total 
Treatment Phase duration of 56 weeks, whichever occurs first.  
Exit DBPCFC: Following completion of the approximately 12-week Maintenance 
Period, subjects will undergo an Exit DBPCFC (to a cumulative maximum of 
2043 mg of peanut protein). Subjects who complete 12 weeks of maintenance and 
fail to tolerate the Exit DBPCFC at 300 mg (443 mg cumulative) of peanut 
protein will not be eligible to enroll in the follow-on study ARC008. 
If ARC008 is not yet available at the study site, subjects may continue blinded 
study treatment and have clinic visits every 4 weeks in ARC010 until ARC008 is 
available. Subjects who do not tolerate 300 mg peanut protein at the Exit 
DBPCFC will not continue blinded study treatment in ARC010.  
Study Procedures 
The following procedures will be performed according to the scheduled visits 
tabulated in Appendix 1: 
• 
Informed consent (and assent, as age appropriate) 
• 
Inclusion/exclusion criteria 
• 
Review of Subject Eligibility Form 
• 
Medical/allergy history  
• 
Concomitant medications 
• 
Contraception review 
• 
Physical examination, including height and weight 
• 
Vital signs (blood pressure, pulse rate, body temperature) 
• 
Peak expiratory flow rate (PEFR) in subjects 6 years and older 
• 
Spirometry (FEV1) in subjects 6 years and older when PEFR shows a 
clinically relevant reduction or the subject shows clinical deterioration 
(eg, active wheeze on physical examination) 
• 
Pregnancy test for females of childbearing potential (FOCBP) 
• 
Diet (food allergen) history 
• 
Blood draw (same venipuncture for all samples) to collect samples for:  
o Peanut- and peanut component-specific IgE, total IgE, and peanut-
specific IgG4 assays  
o Complete blood cell count (CBC)  
o Optional blood sample for immune cell characterization assays 
(separate informed consent required) 
• 
SPT 
• 
IP administration at the CRC  
• 
Dispensing of IP for home dosing/return of unused IP 
• 
Assessment of dose tolerability to decide appropriateness of up-dosing 
or maintenance 
• 
DBPCFC, performed in accordance with PRACTALL guidelines, but 
with the protocol-specified modifications 
• 
Quality of life assessment using the FAQLQ and the FAIM 
questionnaire 

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Protocol ARC010 Synopsis 
Title 
AR101 TRIAL IN EUROPE MEASURING ORAL IMMUNOTHERAPY SUCCESS IN 
PEANUT ALLERGIC CHILDREN (ARTEMIS) 
• 
Assessment of asthma control using the Asthma Control Test 
questionnaire in subjects with asthma 
• 
Assessment of treatment satisfaction using TSQM-9, exit questionnaires, 
and palatability questions  
• 
Monitoring for dosing compliance 
• 
AE monitoring 
• 
Telephone follow-up 
• 
Treatment unblinding 
 

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Protocol ARC010 Synopsis 
Initial Escalation Period, Day 1, Dosing Schedule 
Day 1 
Dose # 
Study Product Dose 
(mg peanut protein or placebo) 
Cumulative Study Product Dose 
(mg peanut protein or placebo) 
1 
0.5 
0.5 
2 
1 
1.5 
3 
1.5 
3 
4 
3 
6 
5 
6 
12 
Doses will be delivered at 20- to 30-minute intervals. 
Subjects who are unable to tolerate a dose of 3 mg at the end of Day 1 will be considered an initial escalation 
failure. 
All subjects who tolerate a dose of at least 3 mg on Day 1 will return on Day 2 to receive a single confirmatory 
3 mg dose under direct observation. 
Subjects with either no symptoms or mild, non-DLS after receiving 3 mg on Day 2 are to start 2 weeks of 
daily dosing at 3 mg. 
Subjects who experience moderate or severe symptoms after receiving the 3 mg dose on Day 2 will be 
considered escalation failures.  
Future dose escalations will occur every 2 weeks with the initial dose increase administered in the CRC. 
 

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Protocol ARC010 Synopsis 
Up-dosing Period Dosing Schedule 
Up-dosing 
Dose # 
Study Product Dose 
(mg peanut protein or 
placebo) 
Interval (weeks) 
% Increase 
1 
3 
2 
 
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 
Enter Maintenance Period 
25% 
Capsules and sachets (introduced during the Maintenance Period) will be opened, contents sprinkled over an 
age-appropriate food, and mixed thoroughly. The 300 mg capsules will be used for at least the first 2 weeks 
of dosing during the 12-Week Maintenance Period. 
 

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TABLE OF CONTENTS 
1. 
BACKGROUND AND RATIONALE .......................................................................... 20 
1.1 
Background ...................................................................................................................... 20 
1.2 
Clinical Trials of AR101.................................................................................................. 22 
1.2.1 
ARC001 Trial .................................................................................................................. 22 
1.2.2 
ARC003 Study ................................................................................................................. 25 
1.2.3 
ARC004 Study ................................................................................................................. 25 
1.2.4 
Open-label Follow-on Study, ARC008 ........................................................................... 25 
1.3 
Rationale for Selection of Study Population .................................................................... 26 
1.4 
Rationale for Selection of Investigational Product Regimen (Dose and Duration) ......... 26 
1.5 
Rationale for the Doses Selected for the DBPCFC ......................................................... 27 
1.6 
Known and Potential Risks and Benefits to Human Participants .................................... 28 
2. 
OBJECTIVES ......................................................................................................... 29 
2.1 
Primary Objective ............................................................................................................ 29 
2.2 
Secondary Objectives ...................................................................................................... 29 
3. 
STUDY DESIGN ..................................................................................................... 29 
3.1 
Screening Period .............................................................................................................. 29 
3.2 
Treatment Phase ............................................................................................................... 30 
3.3 
Exit DBPCFC .................................................................................................................. 32 
3.4 
Open-label Follow-on Study – ARC008 ......................................................................... 33 
3.5 
Definition of End of the Study ......................................................................................... 34 
3.6 
Study Design Safety Considerations ................................................................................ 34 
3.7 
Primary Efficacy Endpoint .............................................................................................. 34 
3.8 
Secondary Endpoints ....................................................................................................... 34 
3.8.1 
Secondary Efficacy Endpoints ......................................................................................... 34 
3.8.1.1 
Key Secondary Efficacy Endpoints ................................................................................. 34 
3.8.1.2 
Other Secondary Efficacy Endpoints ............................................................................... 34 
3.8.2 
Exploratory Endpoints ..................................................................................................... 35 
3.8.3 
Safety Endpoints .............................................................................................................. 35 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS .................................................... 35 
4.1 
Inclusion Criteria ............................................................................................................. 35 
4.2 
Exclusion Criteria ............................................................................................................ 36 
4.3 
Premature Subject Termination from the Study .............................................................. 38 
4.3.1 
Criteria ............................................................................................................................. 38 
4.3.2 
Follow-up of Subjects Who Discontinue Treatment ....................................................... 39 
5. 
STUDY TREATMENT ...................................................................................... 39 
5.1 
Formulation, Packaging, and Labeling ............................................................................ 39 

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5.2 
Preparation, Administration, and Dosage ........................................................................ 40 
5.3 
Investigational Product Accountability ........................................................................... 41 
5.4 
Assessment of Compliance with Study Treatment and Monitoring ................................ 42 
5.5 
Modification of Study Treatment .................................................................................... 42 
5.6 
Concomitant Medications ................................................................................................ 42 
5.7 
Prophylactic Medications ................................................................................................ 42 
5.8 
Rescue Medications for Acute Allergic Reactions .......................................................... 42 
5.9 
Symptomatic Treatment for Chronic and/or Recurrent Adverse Events ......................... 43 
5.10 
Prohibited Medications .................................................................................................... 43 
6. 
STUDY PROCEDURES ............................................................................................ 44 
6.1 
Enrollment and Randomization ....................................................................................... 44 
6.2 
Screening Period .............................................................................................................. 44 
6.3 
Study Treatment Visits .................................................................................................... 46 
6.3.1 
Confirmation of Eligibility and Randomization .............................................................. 46 
6.3.2 
Initial Escalation Period ................................................................................................... 47 
6.3.2.1 
Day 1 ................................................................................................................................ 47 
6.3.2.2 
Day 2 ................................................................................................................................ 48 
6.3.3 
Up-dosing Period ............................................................................................................. 50 
6.3.3.1 
Up-dosing Visits .............................................................................................................. 51 
6.3.3.2 
80 mg Up-dosing Visit ..................................................................................................... 52 
6.3.3.3 
300 mg Up-dosing Visit ................................................................................................... 53 
6.3.4 
Maintenance Period ......................................................................................................... 54 
6.3.5 
Unscheduled Visits / Unscheduled Blood Draws ............................................................ 55 
6.4 
Early Discontinuation Visit ............................................................................................. 55 
6.5 
Exit Visit .......................................................................................................................... 57 
6.6 
Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) ..................................... 58 
6.6.1 
Screening Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) .................... 61 
6.6.2 
Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) ............................. 62 
6.7 
Assessment and Treatment of Allergic Reactions to Peanut OIT .................................... 63 
6.7.1 
Assessment of the Severity of Acute Allergic Reactions to Peanut OIT ......................... 63 
6.7.2 
Assessment of the Tolerability of an Individual Dose of IP ............................................ 63 
6.7.3 
Assessment of the Tolerability of a Dose Level .............................................................. 65 
6.7.3.1 
Assessment of Acute Symptoms Occurring After Dosing............................................... 65 
6.7.3.2 
Assessment of Chronic/Recurrent Symptoms ................................................................. 66 
6.7.4 
Treatment of Acute Reactions to Peanut OIT During Initial Escalation ......................... 66 
6.7.5 
Treatment for Reactions During the Up-dosing Period: Dose Adjustment ..................... 68 
6.7.5.1 
Reactions During the Up-dosing Period .......................................................................... 70 
6.7.5.2 
Reactions to Dosing at Home .......................................................................................... 72 
6.7.5.3 
Temporary Dose Adjustment in Response to Intercurrent Adverse Events .................... 73 

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6.7.6 
Treatment for Reactions During the Up-dosing Period: Pharmacological and Supportive 
Treatments ....................................................................................................................... 75 
6.7.7 
Reactions Occurring During the Maintenance Period ..................................................... 77 
6.8 
Missed Peanut OIT (IP) Doses During Up-dosing .......................................................... 77 
6.9 
Skin Prick Test ................................................................................................................. 80 
6.10 
Assessment of Asthma Control Using the Asthma Control Test Questionnaire ............. 80 
6.11 
Visit Intervals and Windows ............................................................................................ 80 
6.12 
Study Blinding Procedures .............................................................................................. 81 
6.12.1 
Securing Blinding and Randomization Information ........................................................ 81 
6.12.2 
Requirements for Unblinding .......................................................................................... 82 
6.12.3 
Breaking the Blind ........................................................................................................... 82 
6.12.4 
Documenting and Unblinding .......................................................................................... 82 
7. 
SAFETY MONITORING .......................................................................................... 82 
7.1 
Definitions for Recording of Safety Events ..................................................................... 82 
7.2 
Dosing Symptoms as Adverse Events ............................................................................. 83 
7.3 
Definitions ....................................................................................................................... 84 
7.3.1 
Adverse Event (AE) or Medical Event ............................................................................ 84 
7.3.1.1 
Suspected Adverse Reaction ............................................................................................ 84 
7.3.2 
Serious Events (Serious Adverse Events, Serious Suspected Adverse Reactions, or 
Serious Adverse Reactions) ............................................................................................. 84 
7.3.3 
AEs of Interest ................................................................................................................. 85 
7.3.3.1 
Anaphylaxis ..................................................................................................................... 85 
7.3.3.2 
Gastrointestinal AEs Resulting in Prolonged Disruption of Dosing (Events of Interest) 85 
7.3.3.3 
Accidental Food Allergen Exposures .............................................................................. 87 
7.3.3.4 
Adverse Events Featuring a Severe Symptom ................................................................. 87 
7.3.3.5 
Adverse Events Associated with Use of Epinephrine ...................................................... 87 
7.3.4 
Unexpected Adverse Event .............................................................................................. 87 
7.3.5 
Clinically Significant Laboratory Results ........................................................................ 87 
7.4 
Adverse Event Monitoring and Recording ...................................................................... 88 
7.4.1 
Monitoring Procedures .................................................................................................... 88 
7.4.2 
Recording Procedures ...................................................................................................... 89 
7.5 
Data Safety Monitoring Committee ................................................................................. 90 
7.6 
Severity Grading .............................................................................................................. 90 
7.7 
Guidelines for Determining Causality of an Adverse Event............................................ 91 
7.8 
Adverse Event Collection Procedures ............................................................................. 91 
7.8.1 
AE Recording Procedures ................................................................................................ 92 
7.8.2 
SAE Recording and Reporting Procedures ...................................................................... 92 
7.9 
Serious Adverse Event Notification ................................................................................ 93 
7.9.1 
Notifying the Sponsor ...................................................................................................... 93 
7.9.2 
Expedited SAE Reporting to Regulatory Health Authorities .......................................... 93 
7.9.3 
Notifying the Data Safety Monitoring Committee .......................................................... 94 

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7.9.4 
Notifying the Institutional Review Board and Ethics Committee ................................... 94 
7.10 
Other Safety Assessments and Precautions ..................................................................... 94 
7.10.1 
Physical Examination and Vital Signs ............................................................................. 94 
7.10.2 
Prior and Concomitant Medications ................................................................................ 95 
7.10.3 
Pregnancy Testing and Contraception ............................................................................. 95 
7.10.3.1 Pregnancy Testing ........................................................................................................... 95 
7.10.3.2 Contraception ................................................................................................................... 95 
7.11 
Stopping Rules ................................................................................................................. 96 
7.11.1 
Overall Stopping Rules .................................................................................................... 96 
7.11.2 
Individual Stopping Rules ............................................................................................... 97 
8. 
IMMUNE CELL CHARACTERIZATION .................................................................. 97 
8.1 
Peanut-Specific Antibody (Immunoglobulin) Assays ..................................................... 97 
9. 
STATISTICAL CONSIDERATIONS .......................................................................... 97 
9.1 
Analysis Populations ....................................................................................................... 98 
9.2 
Study Endpoint Assessment ............................................................................................. 98 
9.2.1 
Primary Endpoint ............................................................................................................. 98 
9.2.2 
Secondary Endpoints ....................................................................................................... 99 
9.2.2.1 
Analysis of Key Secondary Endpoints ............................................................................ 99 
9.2.2.2 
Analysis of Other Selected Secondary Endpoints ......................................................... 100 
9.2.3 
Supportive Analyses of Primary and Secondary Endpoints .......................................... 101 
9.3 
Subject and Demographic Data ..................................................................................... 101 
9.3.1 
Study Disposition ........................................................................................................... 101 
9.3.2 
Baseline Characteristics and Demographics .................................................................. 101 
9.3.3 
Use of Medications ........................................................................................................ 101 
9.4 
Sample Size and Power Calculations ............................................................................. 101 
10. 
IDENTIFICATION AND ACCESS TO SOURCE DATA ............................................. 102 
10.1 
Electronic Data Capture System .................................................................................... 102 
10.2 
Certification in the Use of EDC System ........................................................................ 102 
10.3 
Data Management .......................................................................................................... 102 
10.4 
Access to Data ............................................................................................................... 102 
11. 
QUALITY CONTROL AND QUALITY ASSURANCE ............................................... 102 
11.1 
Statement of Compliance ............................................................................................... 102 
11.2 
Informed Consent/Assent .............................................................................................. 103 
11.3 
Privacy and Confidentiality ........................................................................................... 103 
12. 
RESOURCE SHARING .......................................................................................... 103 
13. 
PROTOCOL DEVIATIONS .................................................................................... 103 

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13.1 
Major Protocol Deviation (Protocol Violation) ............................................................. 104 
13.2 
Non-Major Protocol Deviation ...................................................................................... 104 
13.3 
Reporting and Managing Protocol Deviations ............................................................... 104 
14. 
REFERENCE LIST ............................................................................................... 105 
 
LIST OF APPENDICES 
Appendix 1: Schedule of Events ................................................................................................. 109 
Appendix 2: Evaluation of Asthma ............................................................................................ 112 
Appendix 3: Criteria for Suspected Diagnosis, and Severity Grading, of Anaphylaxis ............. 113 
Appendix 4: Allergic Reaction Severity Grading ....................................................................... 114 
Appendix 5: Guidance for Determining When an Episode of Anaphylaxis Should Be Reported as 
a Serious Adverse Event (SAE) ............................................................................. 115 
 
LIST OF TABLES 
Table 1 
Initial Dose Escalation Schedule .............................................................................. 31 
Table 2 
Up-dosing Schedule ................................................................................................. 32 
Table 3 
Modified PRACTALL DBPCFC Doses Using Peanut Flour with 50% Peanut 
Protein Content for Screening and Exit DBPCFC ................................................... 60 
Table 4 
Allergy Symptom Severity and IP Dose Tolerability .............................................. 64 
Table 5: 
Treatment(s) for Reactions during the Up-dosing Period by Severity of Reaction . 75 
Table 6: 
Procedure(s) Following Treatment of a Reaction Experienced during the Up-dosing 
Period ....................................................................................................................... 76 
Table 7: 
Adverse Event Recording ........................................................................................ 89 
 
LIST OF FIGURES 
Figure 1 
Study Design ............................................................................................................ 29 
Figure 2 
Schematic for Management of Symptoms Occurring During Initial Escalation 
Day 1 ........................................................................................................................ 67 
Figure 3: 
Schematic for Up-dosing Period Dose Adjustment ................................................. 70 
Figure 4: 
Schematic for Temporary Dose Reductions due to Intercurrent Adverse Events .... 74 
Figure 5: 
Procedures Following Missed Consecutive Doses of Peanut OIT ........................... 78 
 

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List of Abbreviations 
Abbreviation 
Definition 
ACE 
angiotensin-converting enzyme  
ADR 
adverse drug reaction 
AE 
adverse event 
AEI 
adverse event of interest 
ANCOVA 
analysis of covariance  
Aimmune 
Aimmune Therapeutics, Inc. 
ARB 
angiotensin-receptor blockers 
BA/BE 
bioavailability/bioequivalence (studies) 
BP 
blood pressure 
CBC 
complete blood count 
CFR 
Code of Federal Regulations (US) 
CI 
confidence interval 
CODIT™ 
Characterized Oral Desensitization Immunotherapy™ 
CoFAR 
Consortium of Food Allergy Research 
CRC 
clinical research center 
CRF 
case report form 
CT-3 
Communication from the Commission — Detailed guidance on the collection, 
verification and presentation of adverse event/reaction reports arising from 
clinical trials on medicinal products for human use (CT-3, Article 7.4) 
DBPCFC  
double-blind, placebo-controlled food challenge 
DLS 
dose-limiting symptom(s) 
DSMC 
Data Safety Monitoring Committee 
EAACI 
European Academy of Allergy and Clinical Immunology 
EC 
Ethics Committee 
ECG 
electrocardiogram  
EDC 
electronic data capture 
ELISA 
enzyme-linked immunosorbent assay 
EoE 
eosinophilic esophagitis 
ER 
Emergency Room 
FAIM 
food allergy independent measure 
FAQLQ 
food allergy quality of life questionnaire 
FDA 
Food and Drug Administration (US) 
FEV1 
forced expiratory volume in 1 second 
GCP 
Good Clinical Practice 
GERD 
gastroesophageal reflux disease 
GI 
gastrointestinal 
HPLC 
high-performance liquid chromatography  
ICH 
International Council for Harmonisation 

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Abbreviation 
Definition 
ICON 
International Consensus on (anaphylaxis) 
ICS 
inhaled corticosteroid 
IgE 
immunoglobulin E 
IgG 
immunoglobulin G 
IND 
Investigational New Drug  
IP 
investigational product 
IRB 
Institutional Review Board 
ITT 
intent to treat 
IV 
intravenous 
kUA/L 
kilounits of antibody per liter 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg/d 
milligrams per day 
MTD 
maximum tolerated dose 
NCI-CTCAE 
National Cancer Institute’s 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 
PP 
Per Protocol 
PRACTALL 
PRACTical issues in ALLergology, Joint United States/European Union Initiative 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SPT 
skin prick test 
TEAE 
treatment-emergent adverse event 
TSQM-9 
Treatment Satisfaction Questionnaire for Medication 
VITAL 
Voluntary Incidental Trace Allergen Labeling 
 

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1. 
BACKGROUND AND RATIONALE 
1.1 
Background 
Updated background information is provided in the AR101 investigator brochure.   
Peanut allergy is a common and serious condition that disproportionately affects children and 
is commonly associated with severe reactions, including life-threatening anaphylaxis. Peanut 
and/or tree nut allergies account for the majority of fatal food-induced anaphylaxis 
(Sampson et al, 2005). Furthermore, published reports suggest that the prevalence of peanut 
allergy, like other food allergies, has been rising, and is now at high levels, affecting up to 
10% of the population (Branum and Lukacs, 2008; Sicherer et al, 2014). Peanut allergy, 
unlike many other types of food allergy, is usually life-long, with approximately 80% of 
patients remaining peanut-allergic in adulthood.  
The current standard of care in management of food allergy is dietary avoidance of the 
allergenic food, and education of the patient/family in the acute management of an allergic 
reaction. Unfortunately, accidental ingestions remain common, with up to 50% of 
food-allergic patients having at least 1 allergic reaction over a 2-year period (Sicherer et al, 
1998). Furthermore, strict adherence to an avoidance diet can be complicated due to 
difficulty in interpreting food labels (Joshi et al, 2002) and by the presence of undeclared or 
hidden allergens in commercially prepared foods (Altschul et al, 2001; Vierk et al, 2002). 
The burden of avoidance and constant fear of accidental exposure can negatively affect the 
health-related quality of life for both patients and their families (Primeau et al, 2000; Avery 
et al, 2003; Buchanan et al, 2007; Sicherer et al, 2010; Hofmann et al, 2009; Anagnostou et 
al, 2014). 
Despite efforts at strict peanut avoidance, accidental exposure continues to be a major 
concern in peanut allergy because allergic responses can be triggered after ingestion of 
minute quantities of peanut protein. Accidental exposures may result from commercial food 
product mislabeling as well as inattention to, or mistrust of, food warning labels (Vierk et al, 
2007). Foods prepared outside the home, including those encountered in schools, day care 
centers, restaurants, or even the homes of friends and relatives present another ready source 
of accidental exposures. Oftentimes the origin of the accidental exposure remains unknown. 
The threat of accidental exposure and its consequences for patients with peanut allergy and 
their families continues to drive research in the field of food allergy.  
While advances in understanding the causes of food allergy, strategies for food-allergy 
prevention, and the mechanisms underlying tolerance continue to be made, a cure for food 
allergy remains elusive. In the meantime, therapies with the potential to reduce the risk of 
severe allergic reaction in the event of an accidental exposure to an allergenic food continue 
to be developed. An approach that has shown consistently promising results is 
allergen-specific immunotherapy, a therapy that entails administration of increasing amounts 
of an allergen to individuals with IgE-mediated food allergy to raise the threshold and 
decrease the severity of allergic responses to the allergenic food. These allergen-based 
immunotherapies include sublingual, epicutaneous, and most advanced among these, oral 
immunotherapy (OIT).  

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Oral immunotherapy for peanut allergy has been widely studied in recent years and has 
demonstrated encouraging safety and efficacy results in early clinical trials. Additionally, 
beneficial immunologic changes have been shown to occur over time that would tend to 
indicate progression toward a clinical state of sustained desensitization with continued OIT 
(Oppenheimer et al, 1992; Secrist et al, 1995; Nelson et al, 1997; Kapsenberg et al, 1999; 
Lehrer et al, 1999; Frew, 2003; Bousquet, 2004; Wilson et al, 2005; Skripak et al, 2008; 
Jones et al, 2009; Narisety et al, 2009; Blumchen et al, 2010; Kim et al, 2011; Varshney et al, 
2011). 
The goal of Aimmune Therapeutics’ Characterized Oral Desensitization ImmunoTherapy 
(CODITTM) program for peanut allergy is to induce a state of clinically meaningful 
desensitization to peanut protein, where clinically meaningful desensitization is defined as 
the absence of moderate or severe allergic reaction following ingestion of modest, but 
potentially dangerous, amounts of peanut protein. In practical terms, this state of 
desensitization should be sufficient to protect a patient with peanut allergy in case of an 
accidental exposure to peanut while the patient is endeavoring to maintain a peanut-avoidant 
diet.  
It is unfortunately inherent in the nature of accidental exposures that the level of exposure is 
typically unknown. Nevertheless, it is generally believed that most clinically relevant 
accidental exposures to peanut protein occur at low levels. In one well-documented case of 
accidental peanut ingestion, the amount ingested was calculated to be approximately 45 mg 
(McKenna and Klontz, 1997). Moreover, work by French researchers that considered the 
peanut content of a variety of foods and the typical amounts of these foods consumed in 
a serving showed that accidental exposures from peanut-contaminated or mislabeled foods 
are likely to occur at levels below 15 mg of peanut protein (Rimbaud et al, 2013). While 
across the peanut-allergic population the threshold levels at which allergic reactions are 
triggered varies widely, approximately 25% of peanut-allergic individuals would be expected 
to react to 15 mg of peanut protein and 5% to as little as 0.5-1.5 mg, based on a cross-study 
retrospective analysis performed by the Voluntary Incidental Trace Allergen Labeling 
(VITAL) 2.0 study group (Remington, 2013; Allen et al, 2014). Moreover, fully half of the 
peanut allergic population would be expected to have an allergic reaction to no more than 
100-150 mg of peanut protein. Accordingly, protection to the equivalent of 1 whole peanut 
kernel, containing approximately 250-300 mg of peanut protein, should afford a clinically 
meaningful level of protection against many accidental exposures to peanut.  
In the Phase 2 study ARC001, AR101 showed a clinically meaningful level of protection, 
defined as the ability to consume a maximum single dose of 300 mg and a cumulative dose 
of 443 mg in a double-blind, placebo-controlled food challenge (DBPCFC). The ability to 
tolerate this level of peanut protein would be expected to confer protection against a 
life-threatening event should a subject be accidentally exposed to peanut. This level of 
protection was achieved with daily dosing of AR101, a highly characterized, 
pharmaceutical-grade formulation of defatted peanut flour, when administered in a controlled 
OIT regimen. In Study ARC001, 79% of subjects who undertook the OIT regimen were able 
to achieve the target dose of 300 mg/d, after completing an Up-dosing Period that lasted, on 
average, approximately 20 weeks. Following just an additional 2 weeks of maintenance 
therapy at 300 mg/d, all subjects (ie, 23 of the 29 originally randomized to active treatment) 

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were able to tolerate at least 443 mg cumulative of peanut protein with no more than mild 
symptoms in a DBPCFC.  
A peanut-allergic patient’s threshold sensitivity to peanut can vary day-to-day by as much as 
2 orders of magnitude (Glaumann et al, 2013). Also, accidental exposures of up to 1000 mg 
can occur from taking a single, inadvertent bite of a peanut-dense food, such as a peanut 
candy or a peanut butter sandwich. Therefore, in the current Phase 3 study, Aimmune has 
chosen to test if a significantly greater proportion of subjects undergoing OIT to 
a maintenance dose of 300 mg/d of peanut protein as AR101, as compared to placebo, will be 
able to tolerate at least 2043 mg cumulative of peanut protein with no more than mild 
symptoms in a DBPCFC after completing approximately 9 months of treatment.  
1.2 
Clinical Trials of AR101  
Updated information on AR101 clinical trials is provided in the AR101 investigator 
brochure.   
1.2.1 ARC001 Trial 
ARC001 was a multicentre, randomized, double-blind, placebo-controlled study of the 
efficacy and safety of AR101 (characterized peanut allergen) OIT in peanut-allergic children 
and adults (4 to 26 years of age). The study consisted of a Screening Period, including 
a Screening DBPCFC, an initial escalation period, an Up-dosing Period, and a Maintenance 
Period, followed by an Exit DBPCFC.  
All eligible subjects underwent a DBPCFC of up to 100 mg (143 mg cumulative) of peanut 
protein or placebo during the Screening portion of the study. Those subjects who had 
dose-limiting symptoms (DLS) at or before the 100 mg (143 mg cumulative) challenge dose 
of peanut protein (measured as 200 mg of peanut flour) were randomized 1:1 to AR101 or 
placebo.  
Subjects received daily oral dosing of AR101 or placebo OIT; all escalation doses occurred 
in a clinical research center (CRC) or other monitored setting and were administered under 
direct observation.  
After the subjects had been up-dosed to a 300 mg/d dose and had continued to receive that 
dose for 2 weeks, subjects underwent a DBPCFC of up to 600 mg (1043 mg cumulative) of 
peanut protein or placebo.  
All placebo subjects who completed ARC001 were eligible for rollover into the ARC002 
trial. Placebo subjects in ARC002 underwent an escalation and up-dosing schedule identical 
to that for AR101 subjects in the ARC001 protocol. All subjects on AR101 who passed the 
DBPCFC by tolerating ≥ 443 mg cumulative of peanut protein with no more than mild 
symptoms were eligible to proceed to ARC002. Those who did not pass were considered 
treatment failures.  

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Efficacy Results:  
Fifty-six subjects were randomized: 29 subjects to AR101 and 27 subjects to placebo. 
Consent for 1 subject was withdrawn after the subject was randomized but before the first 
dose of study treatment was administered. The intent-to-treat (ITT) population comprised 
55 subjects in total, 29 in the AR101 and 26 in the placebo arm. The 2 study groups were 
overall well matched for baseline characteristics including baseline sensitivity in the 
Screening DBPCFC. Six subjects in the AR101 arm withdrew from the study prior to the 
Exit DBPCFC. 
For the primary efficacy analysis conducted in the ITT population, AR101 was statistically 
significantly superior to placebo, with 23 of 29 (79%) AR101 desensitization responders as 
compared to 5 of 26 (19%) placebo desensitization responders (p < 0.0001 by Fisher’s exact 
test). 
At the time of the Exit DBPCFC, 100% of the 23 AR101 subjects undergoing the DBPCFC 
(Completer population) tolerated 443 mg (cumulative) as compared to 5 of the 26 (19%) 
placebo study completers (p < 0.0001 by Fisher’s exact test). 
At Exit DBPCFC, 18 of 29 (62%) AR101 subjects in the ITT population tolerated 600 mg 
(1043 mg cumulative) versus none of placebo subjects, resulting in a treatment difference of 
62%. Post-hoc analysis by Fisher’s exact test yielded statistical significance (p < 0.0001). In 
the Completer population, 18 of 23 (78%) AR101 subjects and no placebo subjects tolerated 
600 mg at Exit DBPCFC. 
For the key secondary endpoint of the maximum tolerated dose (MTD) with no or mild 
symptoms at the Exit DBPCFC analyzed using a discrete hazard model, AR101 treatment 
was shown to increase the probability of tolerating higher maximum doses with no or mild 
symptoms as compared with placebo treatment. The adjusted probability of tolerating 
300 mg was 0.82 for AR101 and 0.14 for placebo; the adjusted probability of tolerating 
600 mg was 0.59 for AR101 and 0.01 for placebo. Overall, the treatment effect hazard ratio 
(95% confidence interval [CI]) was determined to be 0.10 (0.04, 0.25) (p < 0.0001), 
indicating that the risk of failing the Exit DBPCFC in AR101 subjects was one-tenth the risk 
as compared to placebo subjects. 
The percentage of subjects with a maximum symptom severity grade of moderate or 
severe/worse was lower in the AR101-treated group than in the placebo-treated group at 
every peanut protein level during the Exit DBPCFC. For AR101 subjects, no subject 
experienced a severe/worse symptom during Exit DBPCFC, and moderate symptoms were 
not encountered until a dose of 600 mg was administered. In contrast, at the time of the Exit 
DBPCFC, at least 1 placebo subject experienced moderate or severe/worse symptoms at each 
evaluated dose. 
For the key secondary endpoint of change from baseline in MTD of peanut protein at Exit 
DBPCFC analyzed using an analysis of covariance (ANCOVA) model, a treatment 
difference of 0.912 log10 mg (p < 0.0001) was observed with a change from baseline in MTD 
of 1.254 log10 mg for AR101 and 0.341 log10 mg for placebo. In terms of the ratio of MTD of 

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peanut protein at the Exit DBPCFC compared to baseline, AR101 subjects were able to 
tolerate 17.94 times as much peanut protein at the Exit DBPCFC compared to baseline, while 
placebo subjects were able to tolerate 2.19 times as much peanut protein at the Exit DBPCFC 
compared to baseline. 
For the secondary endpoints of changes in peanut-specific IgE and peanut-specific IgG4 
levels and related measures, the relative treatment effect was calculated as a ratio of 2 ratios 
(study exit result : baseline result in the AR101 group/study exit result : baseline result in the 
placebo group). The largest relative treatment effect, 4.756, was noted for peanut-specific 
IgG4, reflecting study exit values that were 5-times baseline in the AR101 group compared 
to levels that were nearly unchanged in the placebo group. The 95% CI around this relative 
treatment effect (3.271, 6.915) excluded the null value of 1.  
For the secondary endpoint of changes in skin prick test (SPT) results, the difference between 
treatments was calculated as the change from baseline to study exit in the AR101 group 
minus the change from baseline to study exit in the placebo group. At the Exit Visit, a 
notable difference in the change from baseline in maximum peanut SPT wheal diameter was 
observed between treatment groups, with a treatment difference of -5.2 mm. The 95% CI for 
this treatment difference (-9.2, -1.1) excluded the null value of 0. 
Safety Results:  
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 anaphylactic reaction related to treatment. One subject (4%) in the placebo 
group experienced an SAE of presyncope/anaphylaxis related to the peanut protein in the 
Exit DBPCFC (not investigational product [IP]). An additional subject experienced a 
pre-randomization, non-treatment-emergent SAE of anaphylactic reaction following the 
Screening DBPCFC. Four (14%) AR101 subjects discontinued due to adverse events (AEs), 
with either hypersensitivity (n = 3) or vomiting (n = 1). Two additional AR101 subjects 
discontinued due to treatment-related reasons that included gastrointestinal (GI) AEs, but not 
exclusively. No placebo subjects discontinued due to AEs. The most commonly occurring 
TEAE was hypersensitivity, which was reported in 73% of study subjects. The next most 
commonly reported TEAEs were pyrexia (16%), upper respiratory tract infection (13%), 
headache (11%), and vomiting (11%). 
Treatment-emergent AEs classified as an allergic reaction by the investigator occurred in 
71% of subjects. For these treatment-emergent hypersensitivity events, the Medical 
Dictionary for Regulatory Activities (MedDRA) coding indicated that the most common 
preferred terms were vomiting (16%) and abdominal pain (15%). Treatment-emergent 
hypersensitivity AEs were more common in AR101 subjects than in placebo subjects (90% 
vs. 50%, respectively); however, these events tended to be mild or moderate in severity and 
did not typically lead to study withdrawal. 
In summary, AR101 was safe, generally well tolerated, and statistically superior to placebo 
for reducing clinical reactivity to peanut allergen in peanut-allergic children and adolescents 

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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, most notably peanut-specific IgG4 levels, as compared to 
placebo. 
1.2.2 ARC003 Study  
ARC003 (PALISADE) is an international, multicentre, 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 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 are randomized in a 3:1 ratio to receive escalating doses of either AR101 
or placebo. 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 ≥ the 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 has met several times. 
1.2.3 ARC004 Study  
ARC004 is a randomized, controlled, open-label, multicentre study that will explore alternate 
dosing interval regimens during extended maintenance with AR101 in subjects completing 
Study ARC003. The primary objective is to confirm the safety profile of AR101 as measured 
by the incidence of AEs, including SAEs. The secondary objectives include confirmation of 
the efficacy of AR101 through reduction in clinical reactivity; evaluation of the efficacy and 
safety of different AR101 dosing schedules during extended maintenance therapy; evaluation 
of quality of life and treatment satisfaction during AR101 treatment; and evaluation of the 
long-term immunologic effects of AR101 treatment. This study is ongoing. 
1.2.4 Open-label Follow-on Study, ARC008  
The open-label follow-on study ARC008 is designed to accommodate subjects completing 
Aimmune-sponsored studies with AR101. The study is intended to demonstrate the safety of 
AR101 for an extended period (months to years) with the following objectives: unblinded 
expansion of the safety database for AR101, confirmation of the efficacy of OIT with AR101 
up-dosed to a maintenance dose of 300 mg/d of peanut protein in the former ARC010 
placebo population, and to provide an opportunity to the ARC010 trial participants to 
maintain the level of desensitization they may have achieved. 

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1.3 
Rationale for Selection of Study Population 
This study, ARC010 ARTEMIS, will enroll approximately 160 subjects 4 to 17 years of age 
with a history of allergy to peanut or peanut-containing foods. The sample size has been 
selected such that, in combination with the entire clinical experience with AR101 
(eg, ARC001, ARC002, ARC003, ARC004), it is sufficient to assess the efficacy of AR101 
in the relevant subject populations (Section 9.4).  
All subjects enrolled must undergo a Screening DBPCFC to peanut, during which they need 
to react at or before the 300 mg (444 mg cumulative) dosing level of peanut protein 
(measured as 600 mg of peanut flour with approximately 50% protein content) in accordance 
with PRACTALL (Practical Issues in Allergology, Joint United States/European Union 
Initiative) consensus guidelines (Sampson et al, 2012), regardless of how they were initially 
diagnosed as peanut allergic. In spite of the change in dose from 100 mg to 300 mg in 
ARC010, this should continue to select for the more sensitive half of the peanut-allergic 
population (Remington, 2013; Allen et al, 2014), according to a logistical regression analysis 
performed by the VITAL 2.0 study groups using food challenge data from multiple sources.  
This ARC010 Phase 3 study (ARTEMIS) will focus on the age group most likely to be at 
greater risk from accidental exposure (ie, 4 to 17 years of age).  
The lower age limit of 4 years was selected based on epidemiologic child-developmental 
considerations related to feeding behavior (Fallon et al, 1984; Cashdan, 1994; Farrow and 
Blisset, 2012; American Academy of Pediatrics, 2013), as well as practical clinical trial 
execution considerations and safety. 
In the current study, subjects with severe or life-threatening episodes of anaphylaxis or 
anaphylactic shock will be excluded from enrolling only if they have had such an episode in 
the 60 days prior to the Screening DBPCFC, but will not otherwise be prohibited from 
entering the study. This is because peanut-allergic subjects who have had prior 
life-threatening episodes on exposure to peanut can be considered at high risk for another 
such episode, and hence, may be considered precisely the type of subjects who could benefit 
from desensitization therapy. The restriction of 60 days is applied for practical and safety 
reasons, as subjects who have had such a recent episode may be considered to have a 
potentially less favorable benefit-risk ratio for undergoing OIT; and such subjects may be 
reluctant to engage in the study. 
1.4 
Rationale for Selection of Investigational Product Regimen (Dose and Duration) 
For this study, as well as the Phase 3 study ARC003, the dosing regimen used is predicated 
on the dosing regimen successfully used in the Phase 2 studies, ARC001 and ARC002. The 
ARC001 dosing regimen, in turn, was built on the work of the Consortium of Food Allergy 
Research (CoFAR) and its investigators. The basic structure of the dosing regimen consists 
of a single-day initial escalation at very low doses, followed by a build-up phase of dose 
escalations, with a single escalation occurring every 2 weeks, and then an maintenance phase 
at a fixed daily dose. This dosing regimen was shown to be well tolerated and effective in 
previous studies (Burks et al, 2012) and similarly was shown to be well tolerated and have 
clinically important activity in the Phase 2 studies ARC001 and ARC002. 

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The total duration of treatment in the current Phase 3 study will be approximately 9 months 
(approximately 5 months escalation and 3-4 months maintenance at 300 mg/d). The 
up-dosing regimen chosen for the current study was selected based on AR101’s success in 
Phase 2. 
The duration of maintenance therapy prior to testing for clinical efficacy by DBPCFC in the 
current study was similarly selected based on the outcome of the Phase 2 study. The clinical 
trials published to date for peanut OIT have had maintenance periods ranging from 1 to 
7 months, and have demonstrated the ability to allow subjects to tolerate challenge doses 
ranging from 1.25 to 16.7 times their maintenance dose (Clark et al, 2009; Jones et al, 2009; 
Blumchen et al, 2010; Varshney et al, 2011; Anagnostou et al, 2014; Cronin et al, 2014; 
Vickery et al, 2016). The data from the ARC001 and ARC002 Phase 2 studies indicate that a 
clinically meaningful level of desensitization is achieved after up-dosing and just 2 weeks of 
daily maintenance dosing at 300 mg (with > 95% passing DBPCFC at a cumulative 
challenge dose of 443 mg of peanut protein and the majority passing at a 1043 mg 
cumulative challenge) and that extending maintenance dosing from 2 to 14 weeks appears to 
be associated with some improvement in the overall degree of desensitization. Accordingly, 
a blinded Maintenance Period of 3 months is considered sufficient to demonstrate efficacy 
and assess safety in this study. In addition, the ARC003 (PALISADE) Phase 3 confirmatory 
study will provide evidence of safety and efficacy after 6 months’ maintenance therapy; the 
ARC010 (ARTEMIS) will provide complementary confirmatory evidence at 3 months’ 
duration of maintenance, to evaluate whether clinically relevant desensitization in a 
significant proportion of subjects occurs at this shorter time frame.  
The ability to convey to subjects that they are at a therapeutic level of desensitization in a 
reasonable timeframe is an important consideration. Thus, the total duration of blinded 
placebo therapy is limited to a maximum of 56 weeks in this study. 
The data from the ARC001 and ARC002 studies, consistent with previously published 
studies, indicate that the use of a low-dose maintenance phase can provide a clinically 
meaningful level of desensitization that is considerably higher than the daily maintenance 
dose. Three studies in particular (Jones et al, 2009; Cronin et al, 2014; Vickery et al, 2016) 
have specifically reported that daily dosing with 300 mg of peanut protein will allow 
quantities of peanut protein ranging from 2.1 to 5 grams to be tolerated in an oral food 
challenge.  
1.5 
Rationale for the Doses Selected for the DBPCFC 
The study DBPCFCs will be conducted in accordance with the recommended PRACTALL 
guidelines although the Screening DBPCFC will not exceed 300 mg (444 mg cumulative). 
This is to select subjects that are representative of approximately the more sensitive half of 
the peanut-allergic population (Section 1.3). The Exit DBPCFC will not go above a 1000 mg 
(2043 mg cumulative) dose to help ensure subject safety. Additionally, the DBPCFCs will 
progress through the dose levels in an unaltered sequence without repeating any dose to 
provide standardization of the amounts of peanut protein subjects are exposed to when being 
tested in the clinical trial setting. 

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The Exit DBPCFC will initially assess desensitization to 300 mg of peanut; to assess further 
desensitization, subjects will be administered 600 mg peanut protein, and in those shown to 
tolerate this exposure (1043 mg cumulative), an additional dose will be made with 1000 mg 
(2043 mg cumulative). This is equivalent to approximately 8 to 10 peanuts over the course of 
the day.  
The ability to tolerate 1000 mg (2043 mg cumulative) will be assessed as the primary 
endpoint, and the ability to tolerate 600 mg (1043 mg cumulative) and 300 mg (443 mg 
cumulative) will be assessed as key secondary endpoints. As discussed in Section 1.1, all of 
these challenge dose levels are believed to represent amounts of peanut protein in excess of 
what might typically be encountered in an accidental ingestion of peanut. 
1.6 
Known and Potential Risks and Benefits to Human Participants 
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 peanut 
OIT that has been reported in the literature is eosinophilic esophagitis (EoE), affecting an 
estimated 3 to 4% 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 this 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.  
There is no guarantee that participation in this study will help the subject. The subject may 
receive placebo during the double-blind treatment period of the study. Information from this 
study may help researchers to better understand peanut allergy or to develop future tests or 
treatments to help subjects with this condition. 

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Please refer to the current edition of the AR101 Investigator’s Brochure for further 
information regarding the safety profile, risks, and benefits of AR101.  
2. 
OBJECTIVES 
2.1 
Primary Objective 
The primary objective is to demonstrate the efficacy of AR101, a pharmaceutical-grade 
peanut allergen formulation, through reduction in clinical reactivity to limited amounts of 
peanut allergen in peanut-allergic children and adolescents (ages 4 to 17 years, inclusive). 
2.2 
Secondary Objectives 
The secondary objectives are: 
• 
To demonstrate the safety of AR101 as measured by the frequency of AEs, including 
SAEs. 
• 
To evaluate the immunological effects of peanut OIT therapy. 
3. 
STUDY DESIGN 
ARC010 is a European, multicentre, randomized, double-blind, placebo-controlled study. 
The study design is illustrated in Figure 1. 
Figure 1 
Study Design 
 
 
3.1 
Screening Period 
Subjects 4 to 17 years of age must have a clinical history of allergy to peanut or 
peanut-containing foods, a serum IgE to peanut of ≥ 0.35 kUA/L, and/or a SPT to peanut of 
≥ 3 mm versus negative control at the time of Screening. Eligible subjects will undergo an 
initial DBPCFC at the end of the Screening Period (refer to Section 6.6.1). This DBPCFC 

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will include both a peanut challenge (defatted peanut flour) and a placebo challenge 
(artificially peanut-flavored oat flour) on separate days. The Screening DBPCFC will be an 
abbreviated version of the DBPCFC described in the PRACTALL guidelines, with top 
challenge doses of 300 mg (444 mg cumulative) of peanut protein or placebo. 
For each subject, a Blinded Evaluating Physician (Blinded Assessor) is to be designated to 
assess the tolerability of the challenge doses presented in the DBPCFC. The Blinded 
Evaluating Physician, who is assessing and managing subject symptoms on the food 
challenge days, is not to be involved directly in the oversight of study product dosing or the 
assessment or management of AEs during the initial escalation, up-dosing, or maintenance 
phases of the study; nor should he or she be involved in the food challenge material 
preparation on the food challenge days. To the extent practicable, the same Blinded 
Evaluating Physician who determines DLS in the Screening DBPCFC should determine DLS 
in the Exit DBPCFC. 
Those subjects who have DLS at or before the 300 mg (444 mg cumulative) challenge dose 
of peanut protein (measured as 600 mg of peanut flour) will be enrolled into the study. 
According to a logistical regression analysis performed by the VITAL 2.0 study group using 
food challenge data from multiple sources, this would select for the more sensitive portion of 
the peanut-allergic population (Remington, 2013; Allen et al, 2014). Those who successfully 
consume and tolerate a 300 mg (444 mg cumulative) dose of peanut protein during the 
Screening DBPCFC (ie, without manifesting DLS), will be considered screen failures and 
will not be randomized. 
Any subject who is assessed to have had DLS to the placebo part, or both parts, of the 
Screening DBPCFC (ie, to oat flour as well as peanut flour) will be considered a screen 
failure and will not be randomized. 
Approximately 160 subjects who pass Screening will be randomized 3:1 to either AR101 
(active treatment) or placebo using a proprietary interactive response system. 
3.2 
Treatment Phase 
The Treatment Phase comprises 3 periods:  
• 
Initial Escalation (2 consecutive days) – Eligible subjects will be randomized and 
initiate OIT 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 at least a 3 mg dose will be 
considered escalation failures and will be discontinued from the study. Subjects who 
tolerate both the 3 mg and 6 mg doses of IP, or who tolerate the 3 mg but not the 
6 mg dose, will undergo confirmatory testing of the tolerability of a 3 mg dose the 
following consecutive day (refer to Initial Escalation Schedule at end of synopsis). 
Subjects who tolerate this confirmatory dose will enter the Up-dosing Period. 
Subjects who do not tolerate this confirmatory dose will be discontinued. Therapy 
details are found in Section 3 and Section 6 of the protocol.  

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• 
Up-dosing Period – After the initial escalation period, subjects will report to the 
CRC every 2 weeks to escalate their OIT dose to an expected daily dose of 300 mg of 
peanut protein. This constitutes the Up-dosing Period. Subjects will receive daily oral 
dosing of peanut or placebo OIT for approximately 20 weeks, if up-dosing proceeds 
without holding at, or reducing, a dose level; up to 40 weeks, maximum. All 
escalation doses 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). All 
up-dosing activities will be performed under direct observation. Therapy details are 
found in Section 3 and Section 6 of the protocol. 
• 
Maintenance Period – Those subjects who reach the target maintenance dose of 
300 mg/d of IP will enter an approximately 12-week Maintenance Period of 
continued dosing at 300 mg/d, which may be extended by up to an additional 4 weeks 
(for a maximum Maintenance Period duration of 16 weeks), or to a total Treatment 
Phase duration of 56 weeks, whichever occurs first.   
Treatment will be conducted in a double-blind fashion. The IP (AR101 or placebo) will be 
coded according to subject randomization number. The subjects and the investigational site 
personnel will be blinded to treatment assignment. 
The dose-escalation schedule is described in detail in Table 1 and Table 2. 
Table 1 
Initial Dose Escalation Schedule  
Initial Dose 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 
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 a 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. 
 
Subjects who reach and tolerate 300 mg/d will continue at that dose level for the duration of 
the Maintenance Period. The first Maintenance Visit occurs 2 weeks after the 300 mg 
Up-dosing Visit, with visits every 4 weeks thereafter. Any subject unable to achieve a dose 
of 300 mg/d of peanut protein by 40 weeks will not undergo the Exit DBPCFC. 

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Table 2 
Up-dosing Schedule  
Up-dosing Schedule 
Dose Number 
Investigational Product 
Dose, mg (peanut protein 
or placebo) 
Interval (weeks) 
Percent Increase from 
Previous Dose 
1 
3 
2 a 
 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 
Enter Maintenance 
Period 
25 
a Interval includes Day 2 of Initial Escalation. 
During the treatment period, the subjects will be monitored for the tolerability of IP, as 
described in Section 6.7.2 and Section 6.7.3.  
If a subject discontinues therapy prematurely for any reason, the subject will be followed for 
safety and asked to return to the CRC 14 to 16 days following his or her last dose of IP to 
undergo an Early Discontinuation Visit (Section 6.4). 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). Subjects who have GI AEs with prolonged disruption of dosing 
or who discontinue treatment due to GI AEs will have safety follow-up for 6 months or until 
chronic or recurrent GI symptoms resolve or stabilize, whichever is last (Section 7.3.3.2).  
3.3 
Exit DBPCFC 
All subjects who reach the targeted daily dose of 300 mg and maintain that dose through the 
Maintenance Period will undergo an Exit DBPCFC. The Exit DBPCFC will be performed in 
accordance with PRACTALL guidelines, but starting at a dose of 3 mg of peanut protein 
(except for subjects who reacted to 1 mg in their Screening DBPCFC; these subjects will be 
required to start their Exit challenge at 1 mg; Section 6.6.2) and requiring progression in 
a fixed sequence (Table 3), without repeating any dose. Also, the Exit DBPCFC will include 
a 600 mg challenge dose, and the top challenge dose will be capped at 1000 mg.  
The same vehicle food should be used for the Exit DBPCFC as was used for the Screening 
DBPCFC. 

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For each subject, a Blinded Evaluating Physician (Blinded Assessor) is to be designated to 
assess the tolerability of the challenge doses presented in the DBPCFC. The Blinded 
Evaluating Physician, who is assessing and managing subject symptoms on the food 
challenge days, is not to be involved directly in the oversight of study product dosing or the 
assessment or management of AEs during the initial escalation, up-dosing, or maintenance 
phases of the study; nor should he or she be involved in the food challenge material 
preparation on the food challenge days. To the extent practicable, the same Blinded 
Evaluating Physician who determines DLS in the Screening DBPCFC should determine DLS 
in the Exit DBPCFC.  
Each subject will be unblinded after he/she completes the DBPCFC, all major data queries to 
date (ie, queries that could influence allocation to 1 or another analysis population) for the 
subject have been resolved, and the follow-on study ARC008 is available at the study site. 
Subjects may continue blinded study treatment and have clinic visits every 4 weeks in 
ARC010 until ARC008 is available, unless specified otherwise (Section 3.4). To maintain the 
study blind overall, individual unblinding information should only be distributed to 
designated team members on a need-to-know basis as instructed by Aimmune.  
Subjects who do not reach the target dose of 300 mg/d by Week 40 are not eligible for the 
Exit DBPCFC. These subjects will be unblinded once the database has been locked and 
unblinded.  
3.4 
Open-label Follow-on Study – ARC008 
All placebo-treated subjects who complete ARC010 are eligible for rollover into the 
open-label follow-on study ARC008. In ARC008, placebo-treated subjects from ARC010 
will undergo an escalation schedule, starting with the 0.5 mg dose and proceeding 
sequentially through the Up-dosingand Maintenance Periods in an open-label fashion 
identical to that for subjects who received AR101 in the ARC010 study. If subjects tolerate a 
daily dose of 300 mg during the Up-dosing Period, they will enter the Initial Maintenance 
Period. Once 24 weeks in the Initial Maintenance Period have been completed, subjects will 
then enter the Extended Maintenance Period and receive 300 mg/d until the end of the study. 
Subjects will be offered optional annual food challenges. 
All AR101-treated subjects in ARC010 who pass the DBPCFC at the 443 mg cumulative 
dose level of peanut protein (ie, tolerate 443 mg cumulative dose with no more than mild 
symptoms) are eligible to proceed to ARC008. Subjects will receive 300 mg a day for the 
duration of the study, with visits every 3 months to the CRC. They will be offered the 
optional annual food challenges. Subjects who do not pass the DBPCFC at the 443 mg 
cumulative challenge dose level will not be eligible to enroll in ARC008.  
If ARC008 is not yet available at the study site, subjects may continue blinded study 
treatment and have clinic visits every 4 weeks in ARC010 until ARC008 is available. 
Subjects who do not tolerate 300 mg peanut protein at the Exit DBPCFC will not continue 
blinded study treatment in ARC010.  

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3.5 
Definition of End of the Study 
The end of the study is defined as the last visit of the last subject. 
3.6 
Study Design Safety Considerations 
The study design incorporates the following important safety considerations: 
• 
All dose escalations will be performed under direct observation and medical 
supervision in the CRC 
• 
The peanut OIT will start at 0.5 mg and will only escalate to a maximum single dose 
of 6 mg during the initial escalation on Day 1 
• 
AEs, including dosing-related allergic symptoms, whether expected or not, will be 
captured throughout the study 
• 
All subjects and/or their participating family (as appropriate for age and home 
circumstances) will be provided with an epinephrine auto-injector and will be trained 
in its use 
• 
Subjects will be strongly cautioned against consuming any peanuts or peanut-
containing foods other than the IP while on study, and will be instructed to remain on 
a peanut-free diet 
A DSMC will be established and will meet at time points defined in the DSMC charter to 
monitor the study for safety.  
3.7 
Primary Efficacy Endpoint 
The primary clinical efficacy endpoint is the proportion of subjects who tolerate at least 
1000 mg as a single dose (2043 mg cumulative) of peanut protein with no more than mild 
symptoms at the Exit DBPCFC. 
3.8 
Secondary Endpoints 
3.8.1 Secondary Efficacy Endpoints 
3.8.1.1 Key Secondary Efficacy Endpoints 
The key secondary efficacy endpoints are as follows: 
• 
The proportion of subjects who tolerate at least 600 mg as a single dose (1043 mg 
cumulative) of peanut protein with no more than mild symptoms at the Exit DBPCFC  
• 
The proportion of subjects who tolerate at least 300 mg as a single dose (443 mg 
cumulative) of peanut protein with no more than mild symptoms at the Exit DBPCFC 
• 
The maximum severity of symptoms occurring following ingestion of peanut protein 
during the Exit DBPCFC 
3.8.1.2 Other Secondary Efficacy Endpoints 
The other secondary efficacy endpoints are as follows: 

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• 
The MTD with no more than mild symptoms at Exit DBPCFC 
• 
Change from baseline in MTD of peanut protein at Exit DBPCFC 
• 
Use of epinephrine as a rescue medication at Exit DBPCFC and comparison to its use 
at Screening DBPCFC 
• 
Changes in serum peanut- and peanut component-specific IgE, total IgE, and 
peanut-specific IgG4 levels 
• 
Changes in peanut SPT mean wheal diameter 
• 
Quality of life assessments using the food allergy quality of life questionnaire 
(FAQLQ) and the food allergy independent measure (FAIM; van der Velde et al, 
2010) questionnaire 
3.8.2 Exploratory Endpoints 
• 
Treatment satisfaction assessment using the Treatment Satisfaction Questionnaire for 
Medication (the TSQM-9) and an exit questionnaire 
• 
Assessment of palatability (taste and after-taste)  
3.8.3 Safety Endpoints 
• 
The safety of peanut OIT based on AEs and SAEs 
• 
Use of epinephrine as a rescue medication during OIT (Initial Escalation, Up-dosing, 
and Maintenance Periods) 
• 
Frequency and severity of anaphylaxis during OIT (Initial Escalation, Up-dosing, and 
Maintenance Periods), attributable to IP or accidental food exposure 
• 
Frequency and severity of allergic reaction (hypersensitivity) AEs occurring during 
the Up-dosing versus the Maintenance Period, normalized for duration of treatment 
• 
Frequency of accidental ingestion of peanut and other allergenic foods; frequency and 
severity of reactions resulting from accidental ingestion of peanut and other allergenic 
foods 
• 
Frequency and severity of premature discontinuation of dosing due to AEs; and 
frequency of premature discontinuation of dosing due to chronic/recurrent GI AEs 
• 
Assessment of asthma control using the 2007 National Heart, Lung, and Blood 
Institute (NHLBI) classification and the Asthma Control Test questionnaire in 
subjects with asthma 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Inclusion Criteria 
Subjects who meet all of the following criteria are eligible for enrollment as study subjects: 
1. Age 4 through 17 years (inclusive) 
2. Clinical history of allergy to peanuts or peanut-containing foods 

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3. Serum IgE to peanut of ≥ 0.35 kUA/L (as determined by UniCAP™ within the past 
12 months) and/or a peanut SPT wheal diameter ≥ 3 mm compared to control 
4. Experience DLS at or before the 300 mg (444 mg cumulative) challenge dose of 
peanut protein (measured as 600 mg of peanut flour) on Screening DBPCFC 
conducted in accordance with PRACTALL guidelines 
5. Written informed consent from subjects or parent/guardian for all subjects (or both 
parents when required by local authorities) 
6. Written assent from minor subjects as appropriate (in accordance with local 
regulatory requirements) 
7. Use of effective birth control by female subjects of childbearing potential 
(Section 7.10.3.2) 
4.2 
Exclusion Criteria 
Subjects who meet any of these criteria are not eligible for enrollment as study subjects: 
1. History of hemodynamically significant cardiovascular disease, including 
uncontrolled or inadequately controlled hypertension (Section 5.10) 
2. History of severe or life-threatening episode of anaphylaxis or anaphylactic shock 
within 60 days of Screening DBPCFC 
3. 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 including autoimmune diseases and malignancies (including 
malignancies occurring in the 5 years prior to Screening) 
4. 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 
5. Current participation in any other interventional study and/or participation in another 
interventional clinical study within 30 days or 5 half-lives of the IP, whichever is 
longer, prior to randomization  
6. Participation in, and having received active treatment in, any previous clinical study 
of AR101 CODIT 
7. Currently receiving, or having received in the 5 years prior to Screening, any type of 
peanut or any other food immunotherapy clinical study (including subcutaneous, 
sublingual, oral, or epicutaneous)  
8. Subject is in “build-up phase” of immunotherapy to another allergen (ie, has not 
reached maintenance dosing) 
9. Severe asthma (2007 NHLBI Criteria Steps 5 or 6, Appendix 2) 
10. Mild or moderate asthma (2007 NHLBI Criteria Steps 1 to 4), if uncontrolled or 
difficult to control as defined by any of the following: 

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o 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 
spirometry1); or 
o Inhaled corticosteroids (ICS) dosing of > 500 mcg daily fluticasone (or equivalent 
ICS based on NHLBI dosing chart); or 
o 1 hospitalization in the past year prior to Screening for asthma; or  
o Emergency room (ER) visit for asthma within 6 months prior to Screening 
11. History of high-dose corticosteroid use (eg, 1 to 2 mg/kg of prednisone or the 
equivalent for > 3 days) orally or parenterally in any of the following manners:  
o History of daily oral or parenteral corticosteroid dosing for > 1 month during the 
past year; or 
o 1 oral or parenteral corticosteroid course in the past 3 months; or  
o > 2 oral or parenteral corticosteroid courses in the past year ≥ 1 week in duration  
12. Inability to discontinue antihistamines 5 half-lives before the initial day of escalation, 
SPT, or Screening DBPCFC 
13. Lack of an available palatable vehicle food to which the subject is not allergic 
14. Use of any therapeutic antibody (eg, omalizumab, mepolizumab, reslizumab, 
dupilumab, etc.), or any other immunomodulatory therapy excluding aeroallergen or 
venom immunotherapy, or corticosteroids within the past 6 months (Section 5.10) 
15. Use of beta blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, 
angiotensin-receptor blockers (ARB), calcium channel blockers, or tricyclic 
antidepressants (Section 5.10) 
16. Pregnancy or lactation 
17. Residing at the same address as another subject in this or any peanut OIT study 
18. Developing DLS in reaction to the placebo part of the Screening DBPCFC 
19. History of a mast cell disorder, including mastocytosis, urticaria pigmentosa, and 
hereditary or idiopathic angioedema, and chronic spontaneous urticaria or other 
physician-diagnosed physical urticaria syndrome 
20. Allergy to oat 
21. Hypersensitivity to epinephrine or any of the excipients in the IP 
                                                 
1 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. Measures of peak flow will be acceptable for the entry criteria if results are 
> 80% of predicted. 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 investigating physician’s discretion. The attempt must be documented, 
and a clinical assessment is required. 

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22. Any other condition that, in the opinion of the investigator, precludes participation for 
reasons of safety 
23. Inability to follow the protocol requirements 
24. Patients being in any relationship or dependency with the sponsor and/or investigator 
25. Subjects with a history of alcohol, medication or drug abuse 
4.3 
Premature Subject Termination from the Study 
4.3.1 Criteria  
No subject randomized into this trial who discontinues treatment for any reason will be 
replaced.  
Unless required for safety reasons (ie, medical treatment of an SAE), subjects eligible for an 
Exit DBPCFC will not be unblinded to their treatment assignment until after the subject 
completes the Exit DBPCFC and after all major data queries for the subject are resolved, and 
the follow-on study ARC008 is available at the study site. Subjects who are considered 
escalation failures will be unblinded once the trial database has been locked and treatment 
assignment unblinded. 
Any subject will be prematurely terminated from additional study drug treatment and will be 
excluded from any further study procedures (with the exception of safety follow-up) for the 
following reasons: 
1. Life-threatening symptoms (CoFAR Grade 4; refer to Table A4 in Appendix 4), 
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 allergic hypersensitivity symptoms (CoFAR Grade 3; refer to Appendix 4) 
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. Subjects who experience severe 
symptoms (eg, severe nausea, rhinorrhea, or pruritus) that are not life-threatening, not 
requiring intensive therapy, and not associated with any other features indicating a 
serious clinical condition, and who the investigator feels are suitable to continue with 
the study, will be discussed with the medical monitor and may continue the trial 
under close supervision, if both the Investigator and the medical monitor deem it 
appropriately safe to do so 
3. Pregnancy  
4. Non-adherence (non-compliance) with study product 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 
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5. Medically indicated circumstances (eg, as part of the treatment for intercurrent AEs) 
that require missed study product dosing for >14 consecutive days, except for the 
voluntary 30-day hiatus for AEs occurring at or before the 20-mg dose 
6. The subject elects to withdraw consent from all future study activities, including 
follow-up. 
7. The subject is lost to follow-up (ie, no further follow-up is possible because attempts 
to re-establish contact with the subject have failed). 
8. 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. 
9. The subject dies. 
10. Poor control or persistent activation of secondary atopic disease (eg, atopic 
dermatitis, asthma)  
11. Started on ARB, ACE inhibitors, beta blockers, or other prohibited medications, with 
no alternative medications available per the prescribing doctor 
12. The subject develops biopsy-documented EoE 
Subjects who discontinue IP prematurely due to AEs or other safety concerns should be 
encouraged to continue their participation in follow-up safety assessments. 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 
If a subject discontinues therapy for any reason, the subject will be followed for safety and 
asked to return to the CRC for an Early Discontinuation Visit 14 to 16 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 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). 
Subjects who have GI AEs with prolonged disruption of dosing or who discontinue treatment 
due wholly or in part to GI AEs will have safety follow-up for 6 months or until chronic or 
recurrent GI symptoms resolve or stabilize, whichever is last, and be instructed to complete 
the Pediatric Eosinophilic Esophagitis Symptom Scores (PEESSTM v2.0) questionnaire 
(Franciosi et al, 2011) at the time of treatment discontinuation and monthly for 6 months 
(Section 7.3.3.2). Additional instructions for the follow-up of subjects who discontinue 
treatment due wholly or in part to GI AEs are provided in Section 7.3.3.2. 
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, 

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comprising capsules containing 0.5, 1, 10, 20, and 100 mg each of peanut protein. AR101 is 
characterized by its high-performance liquid chromatography (HPLC) fingerprint and by 
specific enzyme-linked immunosorbent assays (ELISAs) performed against key allergenic 
proteins to demonstrate stability and lot-to-lot comparability. Placebos, containing only 
excipients that are color-matched to the peanut flour, will be provided as matching capsules, 
identical to the active capsules. For maintenance dosing, 300 mg of peanut protein are 
provided in sealed, foil-laminate sachets (1 sachet/day). Matching placebo-containing sachets 
are also provided. 
Capsules containing IP will be provided in blister cards assembled into dosing kits. Each 
individual blister of a blister card will contain a single day’s dose of IP; each 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 (Section 3).  
IP will be distributed to subjects/subjects’ parents or guardians by study site 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 IP for the duration of the study. 
5.2 
Preparation, Administration, and Dosage 
The first dose at each new dose level is to be administered in the CRC with 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); once opened, dosing kits cannot be used for any other dosing 
interval or any other subject. At each clinic visit, subjects will receive a kit of capsules or 
sachets to be taken at home according to their specific dose level. The subjects will be 
instructed to document capsules and sachets taken at home using diary logs and to bring all 
unused capsules and sachets 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. 
In exceptional circumstances when a subject is unable to return to the CRC for the next 
scheduled visit (eg, travel, holidays) and continued dosing is necessary, an additional dosing 
kit may be dispensed on a case-by-case basis after submission of a documented request and 
medical monitor approval. One additional dosing kit may be dispensed to continue the 
current dose level if there are no safety concerns in the opinion of the investigator and 
medical monitor (eg, the dose level is tolerated, no intercurrent illnesses) and the subject will 
have access to appropriate emergency medical services as needed. Up-dosing is not allowed 
until the next clinic visit.  
Procedures for preparation and administration of doses given in clinic or at home are the 
same. Dose preparation is to be completed by the subject or supervising adult, as 
age-appropriate. (For in-clinic dosing, dose preparation may be performed by clinic staff or 
by parent/subject 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 

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delivery of contents. The contents of the capsules or the sachets 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 preparing a new dose 
is not feasible, the study product 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, the IP is to be discarded and a new IP dose mixed and consumed. It 
is recommended that each dose of IP be taken at a consistent time (within a 4-hour period) 
each day. A target interval of at least 8 hours should pass between doses.  
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 or 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 baths within 3 hours after dosing). Dosing should 
also not occur within 2 hours of bedtime. Additionally, if a subject has been 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 (Section 6.7), it is crucial that 
subjects take their dose every day, after they commence dosing on Day 1. 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 
Investigational Product Accountability 
Under Title 21 of the Code of Federal Regulations (21CFR §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 IP, including the date and 
quantity of the IP received, to whom the IP was dispensed (subject-by-subject accounting), 
and a detailed accounting of any IP 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 a unique 
subject identifier and the date and quantity of drug dispensed. 
All records regarding the disposition of the IP will be available for inspection by the clinical 
trial monitor. 

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5.4 
Assessment of Compliance with Study Treatment and Monitoring 
Families will document daily dosing and any reaction to at-home dosing using diary logs. 
Central monitoring of dosing compliance will be performed by comparing returned unused IP 
against the daily dosing records.  
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/sachets with the study diary.  
5.5 
Modification of Study Treatment  
As described in Section 6.7, peanut OIT doses may be adjusted by the study site physician if 
the subject is unable to tolerate the scheduled dose level. If such a dose modification occurs, 
the subject will return all kits and unused capsules/sachets of IP during the dose adjustment 
visit, and be dispensed 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, 
SPT, and oral food challenges. Usual topical steroid use is permitted following SPT.  
5.7 
Prophylactic Medications 
None. 
Although symptomatic treatments for chronic/recurrent AEs are permitted (eg, H1 or H2 
histamine blockers, proton pump inhibitors, or inhaled 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 for Acute Allergic Reactions 
Treatment of individual acute allergic reactions during Study ARC010 should be with either 
an antihistamine and/or epinephrine, along with IV fluids, beta-adrenergic agonist 
(eg, salbutamol), oxygen, and/or steroids, as indicated. Subjects and parents/guardians are 
likely already to have an epinephrine auto-injection device, but for those who do not, an 
epinephrine auto-injection device will be provided. The expiry dates for the epinephrine 
auto-injectors will be tracked at the investigational site and subject/families resupplied as 
necessary. Study staff must document in each subject’s medical record that the subject and 
parent/guardian have an unexpired epinephrine auto-injection device and have been trained 
in its proper usage including injection technique.  

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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 may proceed with the symptomatic therapy in place. However, any therapy 
instituted for treatment of symptoms (AEs) related to IP must be withdrawn by 4 weeks prior 
to Exit DBPCFC. If a subject is unable to tolerate a daily maintenance of 300 mg of IP for at 
least the last 4 weeks of dosing prior to Exit DBPCFC free of any symptomatic therapy that 
was initiated during the course of OIT, the subject will be considered a “maintenance failure 
non-responder”. 
5.10 Prohibited Medications 
1. Therapeutic antibodies such as, but not exclusive to omalizumab (Xolair®), 
mepolizumab (Nucala®), reslizumab (Cinqair®), dupilumab (Dupixent®), last used 
within 6 months of Screening 
2. Systemic (oral) corticosteroids used for any greater duration than a total of 
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 
3. Beta blockers (oral) 
4. ACE inhibitors 
5. ARB 
6. Calcium channel blockers 
7. 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; but if an investigator deems use necessary, it 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 one of the study’s medical monitors. 
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 

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prevent transplant rejection, autoimmune disease, and certain neoplasias. Examples include 
cyclosporine, tacrolimus, anti-tumor necrosis alpha drugs, anti-IgE drugs, and anti-IL-5 (or 
IL-5 receptor targeted drugs). If an investigator contemplates the use of a potentially 
immunomodulatory drug during the course of the study, the investigator should discuss this 
with one of the study’s medical monitors prior to initiating use of the drug.  
6. 
STUDY PROCEDURES 
6.1 
Enrollment and Randomization 
Subjects will have an initial Screening DBPCFC consisting of both a peanut challenge and 
a placebo challenge before randomization. The peanut and placebo challenges will be 
conducted in a double-blind fashion, using foodstuffs provided by an unblinded site 
pharmacist, nutritionist, or study coordinator. Those subjects reacting to ≤ 300 mg of peanut 
protein (≤ 444 mg cumulative) will be randomized in a 3:1 ratio to AR101 or placebo. Those 
able to successfully consume the 300 mg (444 mg cumulative) top challenge dose of peanut 
protein during their DBPCFC (ie, do not develop DLS), will not be eligible for the study. In 
addition, those reacting (experiencing DLS) to ≤ 300 mg of the placebo challenge will not be 
eligible for the study. Because of the requirement for the peanut DBPCFC, the Screening 
Period will need to be conducted over more than 1 day. 
Randomization will be performed using a proprietary interactive response system on Day 1 
of the Initial Escalation Period. 
The study procedures are tabulated in Appendix 1 and are listed by visit below. 
6.2 
Screening Period 
Prior to the commencement of any study-related procedures, the investigator, or designee, 
must obtain written informed consent/assent from the subject and parent/guardian (as 
applicable), as described in Section 11.2. The date of signing the consent/assent form is the 
first day of the Screening Period. 
All Screening procedures must be completed no later than 28 days from the signing of the 
consent/assent form. 
Screening will include the following assessments/procedures:  
• 
Informed consent and assent, as age appropriate  
• 
Inclusion/exclusion criteria review 
• 
Review of Subject Eligibility Form 
• 
Medical and allergy history review 
• 
Diet (food allergen exposure) history review 
• 
Concomitant medication review 
• 
Completion of the FAQLQ and FAIM questionnaires anytime during Screening 
before the DBPCFC 

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• 
In subjects with asthma: evaluation of asthma severity using the 2007 NHLBI Criteria 
(Appendix 2) and the Asthma Control Test questionnaire 
• 
Complete physical examination, including weight and height 
• 
Vital sign measurement (BP, pulse rate, body temperature). In addition to initial 
Screening vital sign measurements, vital sign measurements are required just prior to 
each DBPCFC challenge dose or at 15 to 20-minute intervals post-dose, if the 
between challenge dosing interval is longer 
• 
Peak expiratory flow rate (PEFR), performed in all subjects 6 years of age or older, 
measured at approximately the same time for each assessment visit. Three attempts of 
PEFR should be performed, and the best attempt selected. 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 investigating 
physician's discretion. The attempt must be documented, and a clinical assessment is 
required. 
• 
Spirometry* (forced expiratory volume in 1 second [FEV1]), performed when PEFR 
shows a clinically relevant reduction or the subject shows clinical deterioration (eg, 
active wheeze on physical examination); 3 attempts of FEV1 should be performed, 
and the best attempt selected.  
*Only for subjects 6 years of age and older who are able to adequately perform 
spirometry. In order to assess whether the subject is able to adequately perform 
spirometry, the spirometry must be attempted, and any attempt must be documented. 
• 
Serum pregnancy test for females of childbearing potential (pregnancy test result 
must be available prior to the DBPCFC) 
• 
Blood draw (same venipuncture for all samples), at any time during Screening prior 
to the DBPCFC, to collect samples for:  
o Peanut- and peanut component-specific IgE, total IgE, and peanut-specific IgG4 
assays  
o Complete blood cell count (CBC)  
o Optional blood sample for immune cell characterization assays 
The amount of blood to be taken in total for all tests (required immunoglobulin and 
CBC and optional immune cell characterization assays) will be included in the 
manual of procedures and not exceed a total volume of 2.5 mL/kg, to a maximum 
total of 70 mL on any study day. Blood draw should be collected in compliance with 
local laboratory guidelines and testing regulations. Multiple attempts to obtain blood, 
and repeat samples can be collected where necessary for damaged samples or safety 
reasons. 
• 
SPT to peanut extract 
• 
Confirmation subject or subject’s parent or guardian has an unexpired epinephrine 
auto-injector prior to leaving the clinic following Day 1 of the DBPCFC 

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• 
DBPCFC conducted in accordance with PRACTALL guidelines, with assessments 
made by a Blinded Evaluating Physician (Blinded Assessor), as described in 
Section 6.6. 
• 
Monitoring for AEs, including allergic symptoms (Section 6.7) commences from the 
time the consent/assent form is signed 
• 
Subjects will be instructed to continue to follow a peanut-avoidant diet for the 
duration of the study.  
• 
Subjects and parents or 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 When and how to administer epinephrine via auto-injector 
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, including those from the Screening DBPCFC, 
will serve as the baseline measures for comparison to subsequent measures obtained during 
the course of the study. 
6.3 
Study Treatment Visits 
6.3.1 Confirmation of Eligibility and Randomization 
At the end of the Screening DBPCFC assessment, the food challenge materials will be 
unblinded to establish whether any DLS demonstrated by the subject were a result of the 
peanut or the placebo food challenge material. If DLS are established to have occurred as a 
result of (only) the peanut food challenge material the following steps will be taken: 
• 
Assessment that the subject still meets all eligibility criteria – a Subject Eligibility 
Form, which documents subject eligibility, is completed and sent to the medical 
monitor for review 
• 
Medical monitor will review the Eligibility Form and confirm whether the subject is 
eligible to proceed to randomization (within 72 hours of receipt of the completed 
Eligibility Form), if applicable. 
• 
Subject’s Initial Escalation Day 1 visit is confirmed and should occur such that Initial 
Escalation Day 1 is not later than 29 days following the signing of the consent/assent 
form. Any deviation from this window must be discussed with and agreed by the 
medical monitor.  
• 
Before randomization, inclusion and exclusion criteria are reviewed again to confirm 
the subject remains eligible for the study. 

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• 
The randomization day and Initial Escalation Day 1 should ideally be the same date. 
The investigator, or designee, will randomize the subject in the interactive response 
system on Initial Escalation Day 1 prior to the first dose of IP. The exception to this is 
if it is not logistically feasible to randomize a subject and commence initial escalation 
dosing on the same day; in this situation the site may randomize a subject in the 
interactive response system shortly (maximum 3 days) prior to Initial Escalation 
Day 1. 
6.3.2 Initial Escalation Period 
6.3.2.1 Day 1 
The Initial Escalation Day 1 visit should occur within 10 days of the Screening DBPCFC 
Day 2 and must occur within 6 weeks (preferably by Day 29) following signing of the 
consent/assent form. 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 must be available at all times during the CRC dosing visits. Subjects must be 
free from active wheezing or a flare of atopic disease (eg, atopic dermatitis), or suspected 
intercurrent 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 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 
• 
Complete physical examination, including weight  
• 
Diet (food allergen exposure) history update 
• 
Pre-dose vital sign measurement (BP, pulse rate, body temperature) 
• 
PEFR (3 attempts are to be performed, and the best value taken). PEFR should be 
measured at the same time of day for each visit assessment (eg, morning, afternoon, 
evening). 
• 
Administration of IP (AR101 or matching placebo) at the site, 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 shown in Appendix 1.  
• 
Post-dose vital sign measurements (BP, pulse rate) at the following times: 
o Within 15 to 30 minutes post-dose,  
o At 30 minute intervals thereafter and for the duration of the post-dose observation 
period. 

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• 
Monitoring for AEs, including allergic symptoms (below and Section 6.7 and 
Section 7.2) 
• 
Subjects will be reminded to continue to follow a peanut-avoidant diet for the 
duration of the study.  
Subjects may have clear liquids or flavored gelatin 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 90 minutes 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 90 minutes of 
post-dose observation, the subject may be sent home from the CRC.  
• 
If the subject exhibited mild symptoms, the duration of the observation period should 
be extended beyond 90 minutes, if applicable, so that the subject is observed for a 
minimum of 1 hour after resolution of the symptoms. Subject can continue in the 
study. 
• 
For moderate symptoms, the observation period should be extended to a minimum 
of 2 hours after resolution of the symptoms. Subject is to be discontinued as an 
escalation failure. 
• 
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. Subject is to be discontinued as an escalation failure. 
• 
Any subject deemed to have severe symptoms that include hypoxia, hypotension, or 
change in mental status, stage 3 anaphylaxis defined in Appendix 3, 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 DLS occur at or before the 3 mg single dose, there will be no further dosing of IP. 
The subject will be asked to return to the CRC 14 to 16 days following the last dose 
of IP to undergo an Early Discontinuation Visit (Section 6.4). The subject will 
continue to be monitored for safety until the Early Discontinuation Visit is completed 
or any ongoing AEs are resolved, whichever comes first. 
• 
If no DLS occur during Day 1 dose escalation, or if DLS 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. 
6.3.2.2 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 

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immediately following Day 1 is when unforeseen circumstances (eg, an intercurrent illness) 
create a safety risk to provide the next dose, consistent with the rules for missed doses 
(Section 6.8). 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 intercurrent illness prior to continuing with Day 2 of the initial dose escalation.  
The following assessments/procedures will be performed:  
• 
Concomitant medication update 
• 
Symptom-directed physical examination 
• 
Diet (food allergen exposure) history update 
• 
Pre-dose vital sign measurement (BP, pulse rate, body temperature) 
• 
PEFR (3 attempts are to be performed, and the best value taken). PEFR should, as far 
as possible, be measured at the same time of day at each visit (eg, morning, afternoon, 
evening) 
• 
Oral administration of a single 3 mg dose of IP  
• 
Post-dose vital sign measurements (BP, pulse rate) at the following times: 
o Within 15 to 30 minutes post-dose,  
o At 30-minute intervals thereafter and for the duration of the post-dose observation 
period. 
• 
Monitoring for AEs, including allergic symptoms (Section 6.7) 
• 
Subjects will be reminded to continue to follow a peanut-avoidant diet for the 
duration of the study.  
At a minimum, subjects must be observed for 90 minutes 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 90 minutes of post-
dose observation, the subject may be sent home from the CRC.  
• 
If the subject exhibited mild symptoms, the duration of the observation period should 
be extended beyond 90 minutes, if applicable, so that the subject is observed for a 
minimum of 1 hour after resolution of the symptoms. Subject can continue in the 
study. 
• 
For moderate symptoms, the observation period should be extended to a minimum 
of 2 hours after resolution of the symptoms. Subject is to be discontinued as an 
escalation failure. 

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• 
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. Subject is to be discontinued as an escalation failure 
• 
Any subject deemed to have severe symptoms that include hypoxia, hypotension, or 
change in mental status (stage 3 anaphylaxis defined in Appendix 3), 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 DLSs occur on Day 2, there will be no further dosing. The subject will be asked to 
return to the CRC 14 to 16 days following the last dose of IP to undergo an Early 
Discontinuation Visit (Section 6.4). The subject will continue to be monitored for 
safety until the Early Discontinuation Visit is completed or any ongoing AEs are 
resolved, 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 (Day 3), and to continue daily 
home dosing at that dose level for 2 weeks until next escalation. 
• Subjects and parents/guardians will be educated on home dosing instructions per 
Section 5.2.  
On Day 3, the site is to make telephone contact with the subject/subject’s parent or 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.  
6.3.3 Up-dosing Period  
The Up-dosing Period will last approximately 20 (to a maximum of 40) weeks and comprise 
10 scheduled Up-dosing Visits (including the first 300 mg dose of the Maintenance Period), 
with the potential for Unscheduled Visits for assessment of dose tolerability, dose-reduction, 
dose re-escalation, or management of AEs. 
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 intercurrent 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 
intercurrent 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.  

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6.3.3.1 Up-dosing Visits 
The following assessments/procedures are scheduled for each Up-dosing Visit in the CRC: 
• 
Concomitant medication review 
• 
Contraception review 
• 
Diet (food allergen exposure) history update 
• 
Return unused IP 
• 
Symptom-directed physical examination 
• 
Pre-dose vital sign measurement (BP, pulse rate, body temperature) 
• 
PEFR (3 attempts are to be performed, and the best value taken). PEFR should be 
measured at the same time of day for each visit assessment (eg, morning, afternoon, 
evening) 
• 
IP administration under observation in the clinic 
• 
Post-dose vital sign measurements (BP, pulse rate) at the following times: 
o Within 15 to 30 minutes post-dose,  
o At 30-minute intervals thereafter, if the time between doses is extended, and for 
the duration of the post-dose observation period. 
• 
Provide subject with IP for daily dosing until next visit 
• 
Monitoring for dosing compliance  
• 
Monitoring for AEs, including allergic symptoms (below and Section 6.7 and 
Section 7.2) and review of symptoms reported in subject diary 
• 
Subjects will be reminded to continue to follow a peanut-avoidant diet for the 
duration of the study.  
At a minimum, subjects must be observed for 90 minutes 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 90 minutes of post-dose 
observation, the subject may be sent home from the CRC.  
• 
If the subject exhibited mild symptoms, the duration of the observation period should 
be extended beyond 90 minutes, if applicable, so that the subject is observed for 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. 

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• 
Any subject deemed to have severe symptoms that include hypoxia, hypotension, or 
change in mental status (stage 3 anaphylaxis defined in Appendix 3), 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/subject’s parent or guardian to enquire 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.  
• 
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. The investigator may also decide to maintain the current dose or to 
withhold dosing. Guidelines for setting the new, lower dose are outlined in 
Section 6.7.5, 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 6.7. Failure to successfully escalate after 
3 consecutive attempts, with each attempt spaced at least 2 weeks apart, will result in 
the cessation of dosing. The subject will be asked to return to the CRC 14 to 16 days 
following the last dose of IP to undergo an Early Discontinuation Visit (Section 6.4) 
and is to be followed for safety in the interim. 
• 
For symptoms occurring during the Maintenance Period, the same study dosing rules 
and guidelines that apply for the Up-dosing Period will also apply.  
6.3.3.2 80 mg Up-dosing Visit 
The 80 mg Up-dosing Visit is the approximate midpoint of the Up-dosing Period. At the 
80 mg Up-dosing Visit the following procedures are to be performed in addition to those 
performed at the other Up-dosing Visits:  
• Complete physical examination, including height and weight 
• 
In subjects with asthma: evaluation of asthma severity using the 2007 NHLBI Criteria 
(Appendix 2) and the Asthma Control Test questionnaire 
• 
Urine pregnancy test for females of childbearing potential 

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• 
Review home dosing instructions 
• 
Review with subjects and parents or guardians 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 When and how to administer epinephrine via auto-injector 
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)  
6.3.3.3 300 mg Up-dosing Visit 
At this visit the following procedures are to be performed in addition to those performed at 
the Up-dosing Visits:  
• 
Complete physical examination, including height and weight 
• 
In subjects with asthma: evaluation of asthma severity using the 2007 NHLBI Criteria 
(Appendix 2) and the Asthma Control Test questionnaire  
• 
Urine pregnancy test for females of childbearing potential 
• 
Blood draw (same venipuncture for all samples) to collect samples for:  
o Peanut- and peanut component-specific IgE, total IgE, and peanut-specific IgG4 
assays  
o CBC 
o Optional blood sample for immune cell characterization assays 
The amount of blood to be taken in total for all tests (required immunoglobulin and 
CBC and optional immune cell characterization assays) will be included in the 
manual of procedures and will not exceed a total volume of 2.5 mL/kg, to a maximum 
total of 70 mL on any study day. Blood draw should be collected in compliance with 
local laboratory guidelines and testing regulations. Multiple attempts to obtain blood, 
and repeat samples can be collected where necessary for damaged samples or safety 
reasons. 
• 
SPT to peanut extract 
• 
Review home dosing instructions 
• 
Review with subjects and parents or guardians 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): 

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o Recognition of an allergic reaction and of the symptoms of anaphylaxis  
o When and how to administer epinephrine via auto-injector 
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)  
6.3.4 Maintenance Period  
The first Maintenance Visit will occur 2 weeks after the start of dosing at 300 mg/d; 
thereafter, Maintenance Visits will occur approximately every 4 weeks. 
Subjects should withhold their daily home dose of IP on in-clinic dosing days, but should 
take all other prescribed medications as scheduled.  
The following assessments/procedures are scheduled for each in-clinic dosing Maintenance 
Visit in the CRC: 
• 
Concomitant medication review 
• 
Contraception review 
• 
Diet (food allergen exposure) history update 
• 
Return unused IP to the clinic at each visit 
• 
Symptom-directed physical examination 
• 
Pre-dose vital sign measurement (BP, pulse rate, body temperature) 
• 
PEFR (3 attempts are to be performed, and the best value taken). PEFR should be 
measured at the same time of day for each visit assessment (eg, morning, afternoon, 
evening). 
• 
IP administration under observation in the clinic 
• 
Post-dose vital sign measurements (BP, pulse rate) at the following times: 
o Within 15 to 30 minutes post-dose; 
o At 30 minute intervals thereafter, and for the duration of the post-dose 
observation period is extended beyond 30 minutes. 
• 
Provide subject with take home sachets (or capsules, as appropriate) for daily dosing 
until next visit 
• 
Monitoring for dosing compliance  
• 
Monitoring for AEs, including allergic symptoms (below and Section 6.7 and 
Section 7.2) 
• 
Review home dosing instructions (only at first visit in Maintenance Period) 

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• 
Subjects will be reminded to continue to follow a peanut-avoidant diet for the 
duration of the study.  
In the event that dose reduction from the stable dose of 300 mg/d is required during the last 
weeks of the planned 12-week Maintenance Period, the Maintenance Period may be extended 
on an individual basis up to an additional 4 weeks (to a maximum of 16 weeks) or to a 
maximum study duration of 56 weeks, whichever is shorter. The Exit DBPCFC must be 
performed by Study Week 56. Additionally, subjects must maintain a dose of 300 mg/d for at 
least the last 4 consecutive weeks of the Maintenance Period without the use of symptomatic 
therapy to qualify for the Exit DBPCFC. Failure to do so will result in the subject being 
discontinued from the study. 
If dosing is discontinued, the subject will be asked to return to the CRC 14 to 16 days 
following his or her last dose of AR101 to undergo an Early Discontinuation Visit 
(Section 6.4). 
The procedures for dose reduction and re-escalating back to a dose of 300 mg/d in the 
Maintenance Period will follow the same guidelines as for the Up-dosing Period.  
The procedure for monitoring subjects for safety after in-clinic dosing is the same as for 
Up-dosing Visits (Section 6.7.3), except that the initial period of required post-dose 
observation may be shortened to 30 minutes. 
6.3.5 Unscheduled Visits / Unscheduled Blood Draws 
The procedures performed at Unscheduled Visits may include spirometry and any or all of 
those performed at Up-dosing Visits. 
Additionally, if a subject or subject’s parent/guardian declares his or her intention to 
discontinue IP dosing, whether at a scheduled visit or an unscheduled visit, a blood draw 
should be performed for CBC and immunoglobulin assays, and, for subjects who provided 
prior consent/assent, for optional exploratory immune cell characterization samples. If a 
blood draw is performed at this time, it will take the place of the Early Discontinuation Visit 
blood draw. 
6.4 
Early Discontinuation Visit 
Subjects who fail initial escalation or up-dosing, or who prematurely discontinue treatment, 
will return to the site for an Early Discontinuation Visit. An Early Discontinuation Visit is to 
occur 14 to 16 days after the last dose of IP. 
The following procedures will be performed at the Early Discontinuation Visit: 
• 
Concomitant medication review 
• 
Diet (food allergen) history update 
• 
Completion of the palatability questions  
• 
Completion of the FAQLQ and FAIM questionnaires  

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• 
Completion of the TSQM-9 and exit questionnaires 
• 
In subjects with asthma: evaluation of asthma severity using the 2007 NHLBI Criteria 
(Appendix 2) and the Asthma Control Test questionnaire 
• 
Complete or symptom-directed physical examination, including weight and height 
• 
Vital signs (BP, pulse rate, body temperature); if DBPCFC is to be conducted, these 
vital sign measurements should be taken shortly before the first challenge dose 
• 
PEFR, performed in all subjects 6 years of age or older, measured at approximately 
the same time for each assessment visit. Three attempts of PEFR should be 
performed, and the best attempt selected. For subjects 4 or 5 years of age: peak flow 
rates are to be attempted. The attempt must be documented, and a clinical assessment 
is required. Airflow assessment should be measured at the same time of day as for 
prior visit assessments (eg, morning, afternoon, evening). 
• 
Spirometry* (FEV1), performed when PEFR shows a clinically relevant reduction or 
the subject shows clinical deterioration (eg, active wheeze on physical examination); 
3 attempts of FEV1 should be performed, and the best attempt selected.  
*Only for subjects 6 years of age and older who are able to adequately perform 
spirometry.  
• 
Urine pregnancy test for females of childbearing potential 
• 
Blood draw (same venipuncture for all samples) to collect samples for:  
o Peanut- and peanut component-specific IgE, total IgE, and peanut-specific IgG4 
assays  
o CBC 
o Optional blood sample for immune cell characterization assays 
The amount of blood to be taken for all tests (required immunoglobulin and CBC and 
optional immune cell characterization assays) will be included in the manual of 
procedures and not exceed a total volume of 2.5 mL/kg, to a maximum total of 70 mL 
on any study day. Blood draw should be collected in compliance with local laboratory 
guidelines and testing regulations. (For subjects who discontinue early, the blood 
draw at the Early Discontinuation Visit can be foregone if it was performed at the 
time that dosing with IP ceased.) Multiple attempts to obtain blood, and repeat 
samples can be collected where necessary for damaged samples or safety reasons. 
• 
SPT to peanut extract 
• 
Monitoring for AEs, including allergic symptoms (Section 6.7 and Section 7.2) 
Study subjects who discontinue the study before the scheduled Exit Visit will remain blinded 
until the end of the study (final database lock and unblinding), unless emergency unblinding 
is necessary (Section 6.12.3).  

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6.5 
Exit Visit 
Subjects who tolerate 300 mg/d and are maintained at this dose for approximately 12 weeks 
(up to a maximum of 16 weeks, see Section 6.11) will return to the clinic for an Exit Visit. 
The following procedures will be performed at the Exit Visit: 
• 
Concomitant medication review 
• 
Diet (food allergen) history update 
• 
Completion of the palatability questions before the Exit DBPCFC  
• 
Completion of the FAQLQ and FAIM questionnaires after the completion of the Exit 
DBPCFC and unblinding of each subject  
• 
Completion of the TSQM-9 and exit questionnaires after the completion of the Exit 
DBPCFC and unblinding of each subject  
• 
In subjects with asthma: evaluation of asthma severity using the 2007 NHLBI Criteria 
(Appendix 2) and the Asthma Control Test questionnaire 
• 
Complete physical examination, including weight and height 
• 
Vital signs (BP, pulse rate, body temperature) taken shortly before the first DBPCFC 
dose 
• 
PEFR, performed in all subjects 6 years of age or older, measured at approximately 
the same time for each assessment visit. Three attempts of PEFR should be 
performed, and the best attempt selected. For subjects 4 or 5 years of age: peak flow 
rates are to be attempted. The attempt must be documented, and a clinical assessment 
is required. Airflow assessment should be measured at the same time of day as for 
prior visit assessments (eg, morning, afternoon, evening). 
• 
Spirometry* (FEV1), performed when PEFR shows a clinically relevant reduction or 
the subject shows clinical deterioration (eg, active wheeze on physical examination); 
3 attempts of FEV1 should be performed, and the best attempt selected.  
*Only for subjects 6 years of age and older who are able to adequately perform 
spirometry.  
• 
Urine pregnancy test for females of childbearing potential 
• 
Blood draw (same venipuncture for all samples), prior to DBPCFC, to collect samples 
for:  
o Peanut- and peanut component-specific IgE, total IgE, and peanut-specific IgG4 
assays 
o CBC 
o Optional blood sample for immune cell characterization assays 
The amount of blood to be taken for all tests (required immunoglobulin and CBC and 
optional immune cell characterization assays) will be included in the manual of 
procedures and not exceed a total volume of 2.5 mL/kg, to a maximum total of 70 mL 

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on any study day. Blood draw should be collected in compliance with local laboratory 
guidelines and testing regulations. Multiple attempts to obtain blood, and repeat 
samples can be collected where necessary for damaged samples or safety reasons.  
• 
SPT to peanut extract 
• 
Monitoring for AEs, including allergic symptoms (Section 6.7 and Section 7.2) 
In addition to the procedures listed above, eligible subjects will have an Exit DBPCFC 
performed. Eligible subjects are those who tolerate 300 mg/d and are maintained at this dose 
for the approximately 12-week Maintenance Period. Subjects may have a dose reduction but 
must be on a dose of 300 mg/d without symptomatic therapy for the 4 weeks immediately 
preceding the Exit DBPCFC. The Exit DBPCFC is to be conducted in accordance with 
PRACTALL guidelines, with the protocol-specified modifications, as described in 
Section 6.6.2.  
Each subject participating in the study will be unblinded when he/she completes the Exit 
Visit procedures (including the Exit DBPCFC for eligible subjects), all major data queries 
(ie, queries that could influence allocation to 1 or another analysis population) for the subject 
have been resolved, and the follow-on study ARC008 is available at the study site (refer to 
Section 3.3). If the open-label follow-on study ARC008 is not yet available at the study site, 
the subject may continue blinded study treatment and have clinic visits every 4 weeks in 
ARC010 until ARC008 is available. Subjects who complete 12 weeks of maintenance and 
who do not tolerate 300 mg peanut protein at the Exit DBPCFC will not continue blinded 
study treatment in ARC010.  
All AR101-treated subjects who pass the Exit DBPCFC at the 443 mg cumulative dose level 
of peanut protein (ie, tolerate 443 mg cumulative dose with no more than mild symptoms) are 
eligible to proceed to ARC008. All placebo-treated subjects who complete the study are 
eligible for rollover into ARC008.  
6.6 
Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) 
The DBPCFC is to be conducted as 2 challenges, each part on a separate day, using a placebo 
(artificially peanut-flavored oat flour) for 1 challenge and peanut (as defatted peanut flour) 
for the other. The 2 challenge days should be scheduled as closely together as practicable 
(allowing the washout period for antihistamines) and should not be scheduled more than 
7 days apart. The oral food challenge is to be performed under double-blind conditions so 
that neither the subject, nor the subject’s caregiver, nor any of the clinic staff (except the 
unblinded preparer of the challenge foods) knows which challenge contains the peanut or the 
placebo. The same vehicle food should be used for both parts of the DBPCFC. The clinic 
staff may not be unblinded as to the order of the 2 parts (peanut and placebo) of the DBPCFC 
until after completion of the observation period of the second part of the challenge. 
The DBPCFC will consist of administering gradually increasing challenge doses of a peanut 
flour mixture (containing approximately 50% peanut protein) or a placebo (oat) flour 
mixture, mixed in a vehicle food, at 20 to 30 minute intervals. The placebo flour mixture will 
be supplied pre-mixed with a small amount of artificial peanut flavor to provide a reasonable 

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degree of taste-matching of the final placebo/vehicle food mixture to the peanut/vehicle food 
mixture. Additional, non-allergenic, powdered flavoring agents have been added both to the 
peanut and placebo flour mixtures to help further mask the distinctive flavor of peanut. A 
small amount of oat flour has been added to the peanut flour mixture to help match its 
consistency to the placebo flour mixture. Investigational sites will be provided with 
standardized recipes for preparation of the DBPCFC in a separate manual of procedures. 
Prior to performing DBPCFC, the subject must be: 
• 
Clear of antihistamines and other medications that could interfere with the assessment 
of the DBPCFC, for an appropriate length of time (5 half-lives of the antihistamine or 
other medications in question).  
• 
Assessed for an exacerbation of asthma (if asthmatic) as determined by active 
wheezing or a PEFR < 80% of predicted.  
• 
Free from active wheezing, a flare of atopic disease (eg, atopic dermatitis), or 
suspected intercurrent illness prior to DBPCFC.  
• 
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. Subjects should be maintained on their current, or a reduced, dose level of IP 
until their flare of asthma, atopic disease, or intercurrent illness has resolved.  
Oral food challenges will be undertaken under direct medical supervision and with 
emergency medications and trained staff immediately available. The DBPCFC is performed 
by feeding gradually increasing amounts of a suspect allergenic food (in this case, peanut, 
presented as defatted peanut flour) mixed in a vehicle (matrix) food under physician 
observation (Bock and Atkins, 1990; Burks et al, 2012). For this study, a uniform approach 
to food challenge in accordance with the PRACTALL consensus guidelines for DBPCFC 
will be used by all investigational sites. According to the PRACTALL guidelines, the 
challenge doses start at 1 mg and increase in semi-log increments to a maximum dose of 
3000 mg. The DBPCFC dose escalation schedules used in the current study have been 
modified slightly from the PRACTALL recommendations, and are presented in Table 3. 

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Table 3 
Modified PRACTALL DBPCFC Doses Using Peanut Flour with 50% 
Peanut Protein Content for Screening and Exit DBPCFC 
Challenge Doses 
 
Amount of Peanut 
Protein at Each 
Challenge Dose  
(mg) 
Amount of Peanut 
Flour with 50% 
Protein Content 
(mg) 
Cumulative 
Amount of Peanut 
Protein  
(mg)  
at Screening 
Cumulative 
Amount of Peanut 
Protein  
(mg)  
at Exit 
Screening only 
1 
2 
1 
0 (or 1) a  
Screening and Exit 
3 
6 
4 
3 (or 4) 
Screening and Exit 
10 
20 
14 
13 (or 14) 
Screening and Exit 
30 
60 
44 
43 (or 44) 
Screening and Exit 
100 
200 
144 
143 (or 144) 
Screening and Exit  
300 
600 
444 
443 (or 444) 
Exit only 
600 
1200 
- 
1043 (or 1044) 
Exit only 
1000 
2000 
- 
2043 (or 2044) 
a 
For explanation of contingent/optional doses indicated in parentheses refer to Section 6.6.2.  
 
For each subject, a Blinded Evaluating Physician (Blinded Assessor) is to be designated to 
assess the tolerability of the challenge doses presented in the DBPCFC. The Blinded 
Assessor, who is assessing and managing subject AEs on the food challenge days, is not to be 
involved directly in the oversight of study product dosing or the assessment or management 
of AEs during the initial escalation, up-dosing, or maintenance phases of the study; nor 
should they be involved in the preparation of the food challenge material preparation on the 
food challenge days (for details refer to the Masking Plan). To the extent practicable, the 
same Blinded Assessor who determines DLS in the Screening DBPCFC should determine 
DLS in the Exit DBPCFC. 
Vital signs (BP, pulse rate, and body temperature) are to be measured just prior to each 
challenge dose of the DBPCFC or at 15 to 20 minute intervals post-dose, if the between 
challenge-dosing interval is prolonged. Assessment for signs and symptoms of allergic 
reaction is to be performed at the time that vital signs are checked. 
Each part of the DBPCFC is halted when the investigator determines that DLS have 
occurred. Dose-limiting symptoms, in the setting of the DBPCFC, are any symptoms that, in 
the investigator’s assessment, indicate poor tolerability of the last challenge dose 
administered, and preclude safe advancement to the next challenge dose. 
Dose-limiting symptoms, typically objective symptoms (signs), indicate a positive reaction 
and termination of dosing. The criteria for determining if symptoms are dose limiting during 
DBPCFC are the same as for determining whether a specific dose during up-dosing is 
tolerated (Section 6.7) with the exception that even mild symptoms, if they require 
pharmacological treatment, will be considered dose limiting. 
For clarity, a tolerated dose in the context of the DBPCFCs, is defined as a dose that is 
successfully consumed with no more than mild symptoms, not requiring any pharmacological 
treatment, which are consistent with the following criteria: 

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• 
Isolated to a single organ system 
• 
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. 
As with up-dosing, severe symptoms will always be assessed as dose limiting; and moderate 
symptoms, with only rare exceptions (requiring a documented explanation), will also be 
assessed as dose limiting. Mild symptoms, on the other hand, may or may not be assessed as 
dose-limiting (Section 6.7). 
In general, if an investigator is unwilling to advance to the next challenge dose in a DBPCFC 
because of the emergence of allergic symptoms, the last symptom-eliciting challenge dose 
should be considered to have been not tolerated due to DLS. However, exceptions to this 
may occur, as for example if an emotional reaction to continuing the challenge dose 
escalation interferes with the ability to progress the dose escalation to the point where 
convincingly (typically objective) DLS occur. Any such instances must be accompanied by 
an explanation in the CRF.  
On the days that subjects undergo DBPCFCs (Screening and Exit), they must, at a minimum, 
be observed for 2 hours after administration of the last challenge dose, 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 DBPCFC is completed with no symptoms detected after 2 hours of observation following 
the last challenge dose, the subject may be sent home from the CRC. If the subject exhibited 
mild symptoms, the duration of the observation period should be extended to 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. 
On the day following DBPCFC, the site is to make telephone contact with the subject or 
subject’s parent or guardian to enquire 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. 
6.6.1 Screening Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) 
The initial (Screening) DBPCFC for eligibility will consist of administering gradually 
increasing challenge doses of a peanut flour mixture (containing approximately 50% peanut 
protein) or a placebo (oat) flour mixture, mixed in a vehicle food, at 20 to 30 minute 
intervals. The placebo flour mixture will be supplied pre-mixed with a small amount of 
artificial peanut flavor to provide a reasonable degree of taste-matching of the final 
placebo/vehicle food mixture to the peanut/vehicle food mixture. Additional, non-allergenic, 

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powdered flavoring agents have been added both to the peanut and placebo flour mixtures to 
help further mask the distinctive flavor of peanut. A small amount of oat flour has been 
added to the peanut flour mixture to help match its consistency to the placebo flour mixture. 
Investigational sites will be provided with standardized recipes for preparation of the 
DBPCFC in a separate manual of procedures. 
The Screening DBPCFC will be performed in accordance with PRACTALL guidelines, but 
requiring progression in a fixed sequence without repeating any dose. The procedure will 
also be modified in that the highest dose will be capped at 300 mg (444 mg cumulative) 
peanut protein or placebo, as shown in Table 3. Otherwise, the PRACTALL 
recommendations for maintaining safety and assessing symptom severity serve as useful 
guidelines. 
The DBPCFC is to be conducted as 2 challenges, each part on a separate day, using a placebo 
(artificially peanut-flavored oat flour) for one challenge and peanut (as defatted peanut flour) 
for the other. The 2 challenge days should be scheduled as closely together as practicable and 
should not be scheduled more than 7 days apart. The oral food challenge is to be performed 
under double-blind conditions so that neither the subject, nor the subject’s caregiver, nor any 
of the clinic staff (save for the unblinded preparer of the challenge foods) knows which 
challenge contains the peanut or the placebo. The same vehicle food should be used for both 
parts of the DBPCFC. The clinic staff may not be unblinded as to the order of the 2 parts 
(peanut and placebo) of the DBPCFC until after completion of the observation period of the 
second part of the challenge. 
6.6.2 Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) 
The Exit DBPCFC will be conducted in a manner similar to the Screening DBPCFC, but 
starting at a dose of 3 mg of peanut protein (except for subjects who failed their Screening 
DBPCFC at 1 mg), and with the last 3 challenge doses progressing from 300 mg (443 mg 
cumulative) to 600 mg (1043 mg cumulative) and then to 1000 mg (2043 mg cumulative) of 
peanut protein as shown in Table 3.  
The same vehicle food should be used for the Exit DBPCFC as was used for the Screening 
DBPCFC.  
Dosing with food challenge materials should continue on the days between the 2 parts of the 
Exit DBPCFC, according to the same dosing guidelines that apply throughout the 
Maintenance Period. 
Subjects who failed their Screening DBPCFC at the 1 mg challenge dose of peanut protein 
will be required to start the Exit DBPCFC with a 1 mg dose. At the investigator’s discretion, 
a 1 mg dose may be added at the beginning of the escalation (for a maximum cumulative 
dose of 2044 mg peanut protein) of any subject’s Exit DBPCFC. 
Subjects will be considered desensitization responders for the primary endpoint analysis if 
they are able to tolerate an Exit DBPCFC challenge dose of 1000 mg (2043 mg cumulative) 
of peanut protein with no, or only mild, symptoms.  

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6.7 
Assessment and Treatment of Allergic Reactions to Peanut OIT  
6.7.1 Assessment of the Severity of Acute Allergic Reactions to Peanut OIT  
Subjects may develop allergic symptoms during the course of OIT, similar to those that may 
occur 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 consensus report on 
DBPCFC and with the CoFAR grading system for allergic reactions, are provided as a 
general guide. 
Mild symptoms: 
• 
Skin – limited (few) or localized hives, swelling (eg, mild lip edema), skin flushing 
(eg, few areas of faint erythema), or pruritus (eg, causing mild occasional scratching) 
• 
Respiratory – rhinorrhea (eg, occasional sniffling or sneezing), nasal congestion, 
occasional cough, throat discomfort  
• 
GI – mild abdominal discomfort (including mild nausea), minor vomiting (typically a 
single episode), and/or a single episode of diarrhea 
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 
• 
GI – 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  
• 
GI – severe abdominal pain/cramping/repetitive vomiting and/or diarrhea 
• 
Neurological – change in mental status 
• 
Circulatory – clinically significant hypotension (Appendix 3) 
6.7.2 Assessment of the Tolerability of an Individual Dose of IP 
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. 

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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 4 illustrates the likely combinations of symptom severity and tolerability. 
Table 4 
Allergy Symptom Severity and IP Dose Tolerability 
Symptom Severity 
Assessed Tolerability 
None 
Tolerated 
Mild, oropharyngeal symptoms only 
Tolerated 
Mild, meeting pre-defined tolerability criteria (Section 6.7.1) 
Tolerated a 
Mild, not meeting pre-defined tolerability criteria (Section 6.7.1) 
Not tolerated 
Moderate (except for rare exceptions, Section 6.7.1) 
Not tolerated  
Severe 
Not tolerated 
a 
Mild, persistent gastrointestinal symptoms lasting several days may be not tolerated (Section 6.7.3.1). 
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(s), the investigator will be required to assess whether the 
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 studies, 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 as not tolerated. If a 
dose elicits mild symptoms that do not fit all of the above criteria and the dose is assessed to 

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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. However, there may be rare occasions when a dose eliciting 
moderate symptoms could be assessed as tolerated. 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, the symptom would be typically 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: In nearly all cases, 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 6.7.3). 
6.7.3 Assessment of the Tolerability of a Dose Level 
6.7.3.1 Assessment of Acute Symptoms Occurring After 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 the clinic the day 
after the emergence of the symptoms for administration of the next dose 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.  
The recurrence of a mild symptom(s) 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 in Section 6.7.2.  
• 
If the site is notified of mild dose-related symptoms on 4 or more occasions during a 
7-day period, the subject should return 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 should be taken (Section 6.7.5.2).  
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.  

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6.7.3.2 Assessment of Chronic/Recurrent Symptoms  
GI 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 5.9), 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 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/day 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 6.8.) 
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 6.3.3. 
6.7.4 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 2. Explanatory text follows the figure. 
Investigator judgment will be required to determine the best course of action. An Aimmune 
medical monitor will be available at all times to answer any questions or to assist in any 
decisions related to the study protocol. Possible actions are listed below: 
• 
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 

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• 
Treating additionally with epinephrine, beta-agonist, oxygen, IV fluids, and/or 
glucocorticosteroids, as necessary, and discontinuing dose-escalation 
• 
Discontinuation of desensitization protocol  
Figure 2 
Schematic for Management of Symptoms Occurring During Initial 
Escalation Day 1 
 
 
 
• 
Oral/pharyngeal pruritus/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 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 the 
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) 
Dose-Escalation Dose
Oral/pharyngeal pruritus
Time to next dose: 30 to 60 minutes;
Next dose: advance if symptoms 
resolve spontaneously or to treatment 
with no more than 2 doses of 
antihistamine
Severe Symptoms
Moderate Symptoms
Time to next dose: 30 minutes 
Next dose: advance
Treatment as indicated for severe 
reaction, stop escalation and 
discontinue from study
Occurring at 6 mg: Treat as indicated 
for moderate reaction; Subject to 
return for Day 2 dosing at 3 mg
Occurring at ≤ 3 mg: Treat as indicated 
for moderate reaction; stop escalation 
and discontinue from study
Mild Symptoms

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In general, if a subject requires only 1 or 2 doses 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 more than 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 terminate the initial escalation.  
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. 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. 
The medical monitor will answer any questions and assist in any decisions related to the 
study protocol. 
6.7.5 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. The 
following possible actions are at the investigator’s disposal and are considered in greater 
detail in subsequent sections (Section 6.7.5.1, Section 6.7.5.2, and Section 6.7.5.3): 
• 
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.  

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• 
Reducing dose by 1 or 2 dose levels and maintaining the reduced dose level for at 
least 1 to 2 weeks before attempting dose re-escalation – Generally, this should be the 
action taken when a dose that has been observed in the CRC is assessed as not 
tolerated, if a dose elicits moderately severe symptoms, 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 intercurrent 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 
intercurrent 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 1 or 2 dose levels and maintaining the reduced dose level for a 
duration of time recommended by the investigator – this is instituted if epinephrine is 
given to treat a dose-related allergic reaction. The dose reduction is per investigator 
discretion based on the type and severity of symptoms (Section 6.7.6). 
• 
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.  

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6.7.5.1 Reactions During the Up-dosing Period 
If symptoms arise in the clinic after up-dosing, the investigator is to determine whether or not 
the dose was tolerated (Section 6.7.3). The process algorithm for continued dosing after 
dose-related symptoms occur is depicted in Figure 3. Explanatory text follows the figure.  
Dose adjustment after administration of antihistamines and/or epinephrine for dose-related 
allergy symptoms is described in Section 6.7.6.  
Figure 3: 
Schematic for Up-dosing Period Dose Adjustment 
  
 
• 
No symptoms: 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.  
• 
Oral/pharyngeal pruritus: If a subject experiences 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. 
• 
Oral/pharyngeal pruritus: If only oral/pharyngeal pruritus occurs 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. 
Mild Symptoms; uncertain if dose or 
dose level tolerated
Next dose 
at home or 
in CRC, per 
investigator 
Moderate Symptoms = NOT tolerated 
(with rare exceptions)
Mild Symptoms; dose or dose level 
NOT tolerated
Severe Symptoms = NOT tolerated
Dose subject under medical supervision to 
determine tolerability
Split home dose into 2 doses 8-12 h apart 
(only for repeated mild symptoms with home 
dosing)
Reduce dose by 1 or 2 dose levels and 
maintain reduced dose for at least 1-2 weeks 
before attempting dose re-escalation
Hold current dose level for an additional 
1 to 2 weeks before attempting dose escalation
Reduce dose by 1 or 2 dose levels until dose 
tolerated with no or mild symptoms; if mild 
symptoms result, proceed as above
Discuss with the medical monitor.  Reduce 
dose by 2 dose levels if considered safe.  If no 
or mild symptoms (assessed as tolerated) 
result, proceed with dosing at reduced level for 
at least 2 weeks
Next dose 
in CRC
Next dose 
in CRC
Next dose 
in CRC
or
or
or

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• 
Mild symptoms assessed as tolerated: 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 investigating physician’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. (Section 6.7.5.2 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. 
• Mild symptoms indicating uncertainty regarding tolerability: If other mild 
symptoms occur that indicate uncertainty regarding tolerability, the investigator will 
determine whether the subject should receive the next dose in the CRC or at home. If 
the investigator determines that the subject requires medical supervision to determine 
tolerability, the subject will receive the next dose at the CRC. If the investigator 
determines that the subject does not need medical supervision, the procedure will be 
to split the home dose into 2 doses taken 8 to 12 hours apart OR hold the current dose 
level for an addition 1 to 2 weeks OR reduce the dose by 1 or 2 dose levels and 
maintain the reduced dose for at least 1 to 2 weeks before attempting dose re-
escalation. 
• 
Mild symptoms assessed as not tolerated: 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 approximate 1 dose-level reduction at home, with the subject coming to the 
CRC at the earliest date possible). If the reduced dose is assessed as tolerated, the 
subject is to continue on that daily home dose for at least 1 to 2 weeks. 
(Section 6.7.5.2 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. 
• Moderate symptoms: 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. If this reduced dose elicits no allergic 
symptoms (ie, is well tolerated), the subject will continue on that daily home dose 

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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 (above and Figure 3). 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 at least 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 (above and Figure 3). 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 symptom is assessed as tolerated, 
then the actions taken should be the same as for a dose with mild symptoms assessed 
as tolerated. 
• 
Severe symptoms: 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 subject should return to the CRC 
the next day for dosing at a 2-step reduction in dose under observation. 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 at least 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. 
Consult the medical monitor for specific questions related to dose escalation or continuation 
of the same dose that are not answered in the procedures described above.  
6.7.5.2 Reactions to Dosing at Home 
With the occurrence of symptoms of an acute reaction to IP after home-dosing, or any acute 
allergic reaction, subjects or parents/guardians are instructed to call the study site. The 
investigator must then determine whether or not the dose was tolerated (Section 6.7.3). 
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 3).  
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 

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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 6.3.3 for adjusting up-dosing should be followed. Dose 
adjustment after administration of antihistamines or epinephrine for dose-related allergy 
symptoms is described in Section 6.7.6.  
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 confirm whether or not the dose level is tolerated 
• 
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) and follow the 
procedures described in Section 6.7.5.2. 
• 
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, as described in Section 6.7.3.2. 
• 
Discontinuation of dosing 
Any subject who discontinues up-dosing due to severe or repeated allergic reactions to IP 
should have his or her immune cell characterization blood draw and CBC (Section 8) at, or as 
nearly as possible to, the time of the last dose and no later than at their Early Discontinuation 
Visit. 
6.7.5.3 Temporary Dose Adjustment in Response to Intercurrent Adverse Events 
At the investigator’s 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), can be instituted as part of the treatment regimen for an 
intercurrent AE. Also, if a pattern of decreased tolerability of IP during menses is discerned, 
then a temporary dose reduction can be instituted during this time. The procedures for 
temporary dose reduction due to intercurrent AEs are provided in Figure 4. Explanatory text 
follows the figure. 

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Figure 4: 
Schematic for Temporary Dose Reductions due to Intercurrent Adverse 
Events 
Dose reduction maintained ≤ 4 
consecutive days, whether at 
home or in CRC (per investigator’s 
discretion)
Resume pre-reduction dose level with biweekly 
schedule unchanged.
Dose reduction maintained for 5-7 
consecutive days
Dose reduction maintained for 8 to 
14 consecutive days
• Resume dosing at CRC.
• At investigator’s discretion, pre-reduction dose 
may be resumed OR dosing may continue at 
reduced dose.
• Reset biweekly escalation so that subject 
receives ≥ 2 consecutive weeks of treatment at 
assigned dose level (either reduced or pre-
reduction.
• Conduct next escalation attempt at CRC.
• Escalation should be only 1 dose level about the 
reduced dose.
• If the escalation is successful, subject should 
continue dosing at home for a minimum of 2 
weeks, with biweekly schedule reset as 
necessary.
 
Temporary dose reductions for intercurrent 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 (ie, the dose 
level last tolerated) 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 at least 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.  

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Doses of IP may also be withheld at the investigator’s discretion, in response to an 
intercurrent AE. Doses withheld as part of the treatment for an AE constitute a special 
category of missed peanut OIT doses (Section 6.8). 
6.7.6 Treatment for Reactions During the Up-dosing Period: Pharmacological and 
Supportive Treatments 
The treatments for reactions during the Up-dosing Period are summarized by severity of 
reaction in Table 5. 
Table 5: 
Treatment(s) for Reactions during the Up-dosing Period by Severity of 
Reaction 
Reaction Severitya 
Treatment(s) 
Mild acute allergic reactions requiring treatment  
Antihistamines 
Moderate acute symptoms requiring treatment 
Antihistamines and/or epinephrine, as 
indicated 
Severe symptoms  
Epinephrine 
Assessment of severity of reaction is described in Section 6.7.1. Assessment of tolerability of an 
individual dose is described in Section 6.7.2. 
• 
General Approach: 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.  
• 
Generally, severe symptoms will require treatment with epinephrine at a minimum.  
The procedures(s) that should be implemented after treatment of a reaction experienced 
during the Up-dosing Period are summarized in Table 6. An explanation follows the table. 

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Table 6: 
Procedure(s) Following Treatment of a Reaction Experienced during the 
Up-dosing Period  
Treatment Given for a Reaction 
Procedure(s) Following Treatment 
Antihistamines only  
Continue dose escalation 
Epinephrine:  3 or more doses given for 
dose-related allergy symptoms or 
anaphylaxis 
• 
Stop study product dosing 
• 
Subject is to return to the CRC 14 days after the last dose 
of study product for the Early Discontinuation Visit 
(Section 6.4) 
Epinephrine given in CRC 
• 
Stop study product dosing 
• 
Reduce next dose by 1 or 2 dose levels per investigator 
discretion based on the type and severity of the allergy 
symptoms (Section 6.7.5, Figure 3), and administer in the 
CRC 
• 
After continuing the reduced dose after a duration of time 
recommended by the investigator, dose re-escalation at 
1 dose level may be attempted in the CRC 
• 
Following severe allergy symptoms, discussion with the 
medical monitor is strongly recommended  
Epinephrine given at home 
• 
Instruct subjects to go to the nearest emergency 
department immediately 
• 
Reduce next dose by 1 or 2 dose levels per investigator 
discretion based on the type and severity of the allergy 
symptoms (Section 6.7.5, Figure 3), and administer in the 
CRC under medical supervision prior to resuming any 
dosing at home 
• 
Following severe allergy symptoms, discussion with the 
medical monitor is strongly recommended 
CRC=clinical research center. 
• 
Antihistamines 
If a subject receives antihistamines only, the dose escalation can be continued. If 
symptoms during an up-dosing day require administration of more than 2 doses of an 
antihistamine or of an antihistamine in combination with other medications (except 
epinephrine), there should be a dose reduction of 1 or 2 dose levels, with the next 
dose given in the CRC. 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 3 or more doses of epinephrine 
will halt all further dosing of IP for the individual. The subject will be asked to return 
to the CRC 14 to 16 days following the last dose of IP to undergo an Early 
Discontinuation Visit (Section 6.4). 
• 
Epinephrine – Clinic 
If administration of epinephrine is required during, or after, a dose-escalation in the 
clinic, or for anaphylaxis, no further dosing of IP is to occur at that visit. The next 

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dose of IP is to be reduced by 1 or 2 dose levels per investigator discretion based on 
the type and severity of allergy symptoms (Section 6.7.5, Figure 3), and administered 
in the CRC. After continuing the reduced dose for a duration of time recommended 
by the investigator, dose re-escalation at 1 dose level may be attempted in the CRC.   
If epinephrine is administered for severe allergy symptoms, discussion with the 
medical monitor is strongly recommended.  
If administration of epinephrine is required a third consecutive time, no further dosing 
should be attempted. Dosing in these subjects will be discontinued. They will be 
asked to return to the CRC 14 to 16 days following their last dose of IP to undergo an 
Early Discontinuation Visit (Section 6.4). 
• 
Epinephrine – Home 
Administration of epinephrine outside of the clinic should be followed immediately 
by the subject being taken to the nearest ER. The subject should return to clinic for a 
reduced dose (dose reduced by 1 or 2 dose levels per investigator discretion), 
administered under medical supervision prior to resuming any dosing at home. After 
continuing the reduced dose for a duration of time recommended by the investigator, 
dose re-escalation at 1 dose level may be attempted in the CRC.   
If epinephrine is administered for severe allergy symptoms, discussion with the 
medical monitor is strongly recommended.   
6.7.7 Reactions Occurring During the Maintenance Period  
This phase consists of the subject receiving the 300 mg/d dose of IP for approximately 
12 weeks. For any noted symptoms during the Maintenance Period, the same IP dosing 
guidelines and procedures will be followed as for the Up-dosing Period. 
6.8 
Missed Peanut OIT (IP) Doses During Up-dosing 
Risk due to missed doses of study product is believed to be highest during the Up-dosing 
Period. The procedures to be followed after missed consecutive doses of study product 
during the Up-dosing Period is depicted in Figure 5. Explanatory text follows the figure. 

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Figure 5: 
Procedures Following Missed Consecutive Doses of Peanut OIT  
Miss 1 dose
• Next dose: current dose, which  may 
be given at home
Miss 2 consecutive doses
Miss 5 to 7 consecutive doses
• Miss  >7 consecutive days of dosing 
due to non-compliance (vs. due to AE 
or IP dispensing error)
• Miss 3 consecutive days of dosing on 
3 occasions (considered excessive 
missed dosing) during Up-dosing
• Miss 3 doses during Maintenance
• Next dose: currently administered 
dose; could be taken at home
• Next dose: ~50% of last tolerated dose, given 
at CRC
• Escalation (if above dose is tolerated): 1 dose 
level weekly (no less frequently than weekly 
and generally no less than every 4 weeks) 
until subject is returned to dose level at which 
lapse occurred
• If symptoms occur during escalation, follow 
Up-dosing guidelines  
• Discontinue dosing
• Subject returns to CRC 14 days after last 
dose for Early Discontinuation Visit
Miss 3 consecutive doses
• Next dose: currently administered 
dose, given at CRC
Miss 4 consecutive doses
• Next dose: currently administered 
dose, given at CRC
• IP held for 8 to 14 consecutive 
days as treatment for AE or 
due to IP dispensing error
• Reinitiate dosing at ~25% of last tolerated dose.
• If lapse occurred during Maintenance, reinitiate dose 
(at investigator’s discretion) at 50% of last tolerated 
dose
• Administer the reduced dose at CRC
• If reduced dose is tolerated, resume dose escalation 
with dose increases of 1 dose level occurring no 
more frequently than weekly and no less frequently 
than every 4 weeks until subject has returned to 
dose level at which lapse occurred
• If symptoms occur during dose-escalation, follow 
Up-dosing guidelines
• IP held >15 consecutive days for any 
reason at any point in the study 
(except for dosing hiatus due to 
chronic/recurrent GI AEs at or 
before 20-mg dose)
• Discontinue dosing
• Subject returns to CRC 14 days after last 
dose for Early Discontinuation Visit
 
AE= AE; GI=gastrointestinal; CRC=clinical research unit; IP=investigational product 

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• 
Miss 1 dose – The next dose would be at the current dose level and could be given at 
home. 
• 
Miss 2 consecutive doses – The next dose would be the current dose level and could 
be given at home. 
• 
Miss 3 consecutive doses – The next dose would be the current dose and would be 
given under supervision in the CRC. 
• 
Miss 4 consecutive doses – The next dose would be the current dose and would be 
given under supervision in the CRC. 
• 
Miss 5 to 7 consecutive doses – Initiate the next dose at approximately 50% of the 
last tolerated dose (to the nearest feasible available whole dose that is ≤ 50% of the 
last tolerated dose). 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 asked to return 
to the CRC 14 to 16 days following their last dose of IP to undergo an Early 
Discontinuation Visit (Section 6.4). 
• 
Additionally, excessive missed dosing, defined as 3 consecutive days of missed 
doses on 3 occasions during the Up-dosing Period or on 3 occasions during the 
Maintenance Period, 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 asked to return to the CRC 14 to 16 days following 
their last dose of IP to undergo an Early Discontinuation Visit (Section 6.4). 
• 
If IP has been withheld for 8 to 14 consecutive days as treatment for an AE or due to 
a IP dispensing error, dosing may be reinitiated at approximately 25% of the last 
tolerated dose (to the nearest feasible available whole dose that is ≤ 25% of the last 
tolerated dose) if the lapse in dosing occurred during the Up-dosing Period. If the 
lapse in dosing occurred during the Maintenance Period, dosing may, at the 
investigator’s discretion, be reinitiated at 50% of the last tolerated dose (to the nearest 
feasible available whole dose that is ≤ 50% of the last tolerated dose). 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 6.7.3.2), the subject will be asked to 
return to the CRC 14 to 16 days following their last dose of IP to undergo an Early 
Discontinuation Visit (Section 6.4). 

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No attempt should be made to make up for a missed dose if greater than 6 hours have elapsed 
since usual time of dosing. 
6.9 
Skin Prick Test 
Subjects will have SPTs performed using investigational site- and sponsor-approved 
procedures for food allergens. Detailed instructions for performance of the SPT will be 
provided in a manual of operating procedures. In brief, while 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 peanut allergen extract 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.  
6.10 Assessment of Asthma Control Using the Asthma Control Test Questionnaire 
Subject or subject and parental assessment of asthma control will be performed at the 
specified visits using the Asthma Control Test questionnaire for subjects with asthma. 
6.11 Visit Intervals and Windows  
Screening 
The Screening Period assessments should be completed within 28 days (Day -27 to Day 0). 
Initial Escalation 
The Initial Escalation Day 1 visit occurs within 10 days of the second day of the Screening 
DBPCFC and must occur within 6 weeks of signing of the consent/assent form (preferably by 
28 days). The exceptions to this are if a subject experiences an AE as a result of the 
DBPCFC, or due to scheduling difficulties, in which case an extension to the Screening 
window should be agreed with the medical monitor.  
Up-dosing Period 
For all Up-dosing Visits, which occur every 2 weeks, there is a ± 3-day visit window. 
Regardless of visit intervals subjects must continue with daily dosing of IP. 
Maintenance Period 
The Maintenance Period lasts for approximately 12 weeks but may be extended up to a 
maximum of 16 weeks or to a maximum of study duration of 56 weeks, whichever is shorter 
(Section 6.3.3.3). There is a ± 3-day visit window for all visits in the Maintenance Period. 
The first Maintenance Visit is 2 weeks after the 300 mg Up-dosing Visit. The next 3 visits 
are at 6, 10, and 12 weeks after the 300 mg Up-dosing Visit. If at 12 weeks after the 300 mg 
Up-dosing Visit the subject has maintained a dose of 300 mg/d for approximately 12 weeks, 
without the use of symptomatic therapy for at least the last 4 weeks, the Exit Visit will be 
performed. If that is not the case, then the subject will continue in the study for up to 4 more 
weeks of 300 mg dosing before proceeding to the Exit Visit.  

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Exit Visit 
The Exit Visit will occur after 12 to 16 weeks after a subject commenced dosing at 300 mg/d.  
Early Discontinuation Visit 
An Early Discontinuation Visit should occur 14 to 16 days from the last dose of IP. 
Unscheduled Visits 
Unscheduled Visits may occur at any time during the study. 
6.12 Study Blinding Procedures 
This is a double-blind study. The study as a whole will not be unblinded until after the last 
subject exits ARC010 and the database is locked. 
After undergoing the Exit DBPCFC, most subjects will, however, become de facto unblinded 
to their on-study treatment assignment on the basis of their experience with the food 
challenge (ie, subjects who fail 1 part of the Exit DBPCFC early on may reasonably deduce 
that they had been in the placebo arm of the study), and those who tolerate both parts of the 
Exit DBPCFC (or fail 1 part only at the highest dose levels tested) may reasonably deduce 
that they had been in the AR101 arm. Hence, the study is double-blinded on an individual 
subject basis only up to completion of the Exit DBPCFC. It is for this reason that assessment 
of reactions to DBPCFC will be made by a Blinded Evaluating Physician (Blinded Assessor).  
The risk of bias being introduced into the determination of DLS during DBPCFCs will be 
substantially reduced by having the assessment of the DBPCFC results made by a Blinded 
Evaluating Physician (Blinded Assessor) who is not otherwise directly involved, during the 
treatment phase, with the treatment of the subjects he or she is evaluating.  
Additionally, to ensure that allocation of subjects to their appropriate analysis populations is 
not biased by knowledge of their treatment assignments, specific masking procedures have 
been put in place to shield study team members who could be involved in determining 
allocation of the subjects to the analysis populations from knowing subject treatment 
assignments (refer to Masking Plan). To further ensure that allocation of subjects to their 
appropriate analysis populations is performed in an unbiased way, subjects will not be 
informed of their on-study treatment assignments or rollover into the open-label follow-on 
study until all major data queries (ie, queries that could influence allocation to 1 or another 
analysis population) have been resolved (as detailed in the Masking Plan).  
Subjects who discontinue the study prior to the Exit DBPCFC are not unblinded until after 
database lock and unblinding of the study as a whole.  
6.12.1 Securing Blinding and Randomization Information 
Aimmune or one or more of its contractors will manufacture, package, label, store, and 
distribute the IP. During site visits, the site monitor will check the clinic and/or pharmacy 

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logs to ensure that appropriate randomization assignments are received, recorded, and 
maintained.  
6.12.2 Requirements for Unblinding  
Prior to the Exit DBPCFC assessment, a subject may be unblinded only when needed for 
making medical decisions regarding the care of a subject. In the event of such a medical 
emergency, the investigator is able to make the decision to unblind a subject, but is 
requested, where possible, to discuss this with the sponsor’s medical monitor. If a 
life-threatening event occurs, the subject should be treated as if the subject received active IP. 
For all non-life-threatening events that require unblinding (eg, AE which may result in 
persistent or significant disability/incapacity), the investigator may contact the clinical 
monitor who will coordinate with the sponsor’s representatives. 
6.12.3 Breaking the Blind 
Site personnel or other study team members (such as the medical monitor) may request 
emergency unblinding as described in Section 6.12.2. 
In case emergency unblinding is necessary, the interactive response system allows study 
personnel with appropriate permissions to request unblinding for a specific subject. An 
automated notification is then sent to the sponsor and the sponsor’s safety designees to 
inform them of the unblinding. A built-in audit trail documents the unblinding process and 
the persons involved. In the event that the interactive response system is not available, a 
phone number is provided to all sites in the interactive response system manual for use in the 
situation of emergency unblinding. Unblinding is possible 24 hours a day, 7 days a week. 
6.12.4 Documenting and Unblinding  
Any premature unblinding requires a full written account by the site study physician of the 
event(s) that necessitated unblinding of the study medication for an individual participant. 
This account includes the reason(s) for unblinding, the name of the sponsor’s medical 
monitor who was notified of the unblinding, the names of the unblinded individual staff 
members, and the date and time the unblinding occurred. The treatment assignment is 
confidential and should not be provided to blinded team members. 
7. 
SAFETY MONITORING 
This section defines the types of AEs 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 at time points defined in the DSMC 
charter. 
7.1 
Definitions for Recording of Safety Events 
All safety events observed under this protocol are captured throughout the duration of the 
study. Some safety events arising under certain defined conditions are recorded on specific 
forms as follows.  

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• 
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 recorded on an AE form in the CRF (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.  
• 
Safety events related to accidental food exposure are recorded on an Allergic AE 
form. They are not to be reported on an AE form (to avoid duplicate reporting) unless 
the event is considered an SAE, as defined below (Section 7.3.2).  
• 
For any event occurring after the informed consent/assent form has been signed that 
meets the definition of anaphylaxis (Appendix 3), an Allergic AE form will be 
completed and forwarded to the drug safety vendor within 24 hours of its occurrence 
and/or the site’s being notified of the event (Section 7.3.3.1).  
• 
If any safety event meets the definition of an SAE (whether or not related to dosing), 
it will also be recorded on an SAE paper/pdf form (in addition to the CRF form). 
With the exception of an anaphylaxis event that is also an SAE, the Anaphylaxis form 
should be completed and the ‘SAE’ box on this form checked. 
• 
SPT reactions are not considered AEs unless the reaction, or a complication from the 
procedure, is considered an SAE, as defined below (Section 7.3.1.1).  
• 
Food challenge reactions that occur in the clinic are captured on study specific forms 
and are not reported on an AE form (to avoid duplicate reporting) unless the event is 
considered an SAE, as defined in Section 7.3.1.1.  
o As IP is not used in the DBPCFCs, no AEs occurring from Screening DBPCFC 
can be treatment-related (referring to treatment with IP).  
o For food challenge reactions that occur at the Exit DBPCFC, it will also usually 
be the case that IP was not the cause of the reaction, as IP is not used in the 
challenge. There is, however the possibility that dosing with IP in the days prior 
to Exit DBPCFC could contribute to a reaction encountered during the challenge. 
The investigator must determine if dosing with IP in the days prior to Exit 
DBPCFC likely contributed to any observed reaction. If so, the investigator 
should indicate the level of the relatedness, and provide a brief explanation as to 
the manner in which prior dosing with IP was thought to be contributory. 
• 
All SAEs are reported on the AE/SAE form (in the CRF) set in addition to the Skin 
Prick Test form or an Oral Food Challenge form if the event occurred during 1 of 
these procedures. All other safety events that occur throughout the study are reported 
on the AE/SAE form set. 
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 7.8.1).  

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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 CRF. For each symptom, the AE CRF will query 
‘Is this an allergic reaction?’ and the site should indicate yes or no accordingly. 
7.3 
Definitions 
7.3.1 Adverse Event (AE) or Medical Event 
An AE is any untoward medical occurrence in humans, whether or not considered IP related 
which occurs during the conduct of a clinical trial. Any change in clinical status, 
electrocardiograms (ECGs), routine labs, x-rays, physical examinations, etc., that is 
considered clinically significant by the study investigator is considered an AE.  
An adverse reaction is any AE caused by the IP.  
In addition, any pregnancy diagnosed in a female subject during treatment with an IP will be 
collected. The pregnancy will be reported as described in the AE Completion Guidelines 
within 24 hours of knowledge of the pregnancy. 
7.3.1.1 Suspected Adverse Reaction 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the 
IP caused the AE. A reasonable possibility implies that there is evidence that the IP caused 
the event. 
7.3.2 Serious Events (Serious Adverse Events, Serious Suspected Adverse Reactions, 
or Serious Adverse Reactions)  
An SAE including a serious suspected adverse reaction or serious adverse reaction as 
determined by the investigator or the sponsor is any event that results in any of the following 
outcomes: 
1. Death 
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.)  
3. Inpatient hospitalization or prolongation of existing hospitalization  
4. Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions  
5. Congenital abnormality or birth defect 
6. 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 1 of the outcomes listed in the above definition of serious event.  

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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 5. 
7.3.3 AEs of Interest 
7.3.3.1 Anaphylaxis 
The definition of anaphylaxis that has been adopted for this study is from the 2014 position 
paper by the European Academy of Allergy and Clinical Immunology (EAACI) Food 
Allergy and Anaphylaxis Guidelines Group (Muraro et al, 2007), that in turn was based on 
the publications of Simons et al. (2011) and Johansson et al. (2004), and is consistent with 
the recently published “International consensus on (ICON) anaphylaxis” (Simons 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 Food and Drug Administration (FDA) Guidance for Industry and 
Investigators, “Safety Reporting Requirements for INDs and BA/BE Studies,” (BA/BE = 
bioavailability/ bioequivalence) 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 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 (Section 7.6 and Appendix 3). 
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 Management of Anaphylaxis (Sampson et al, 2006) (Appendix 3). These 
criteria were again affirmed in the recently published “International consensus on (ICON) 
anaphylaxis” (Simons et al, 2014). 
7.3.3.2 Gastrointestinal AEs Resulting in Prolonged Disruption of Dosing (Events of 
Interest) 
Gastrointestinal AEs, typically chronic/recurrent GI AEs, that result in a prolonged 
disruption of dosing will be considered AEs of interest (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 (Section 6.7) 

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• 
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 6.7.3.2); 
• 
Any subject who permanently discontinues dosing due to GI AEs (Section 4.3.1).  
Subjects who fall into any of these 3 categories will be asked to fill out the PEESS v2.0 
questionnaire, with the assistance of a parent or guardian, as appropriate, while symptomatic, 
at the time of treatment discontinuation, and then every month for 6 months thereafter. 
During the 6-month safety follow-up, subjects may complete the PEESS v2.0 at home and 
send it to the clinic, or they may complete it at the clinic if monthly clinic visits are required.  
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 (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 are to be 
requested to return to the clinic for evaluation monthly for at least 6 months (if the subject is 
asymptomatic, telephone follow-up with a physician 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 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. 
As is the case for any AE occurring during the study, for chronic/recurrent GI AEs 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.  

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7.3.3.3 Accidental Food Allergen Exposures 
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 7.3.1.1, in which case the SAE 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. 
7.3.3.4 Adverse Events Featuring a Severe Symptom 
Any AE meeting the criteria for severe as defined in Section 7.6 will be reported as an AEI. 
7.3.3.5 Adverse Events Associated with Use of Epinephrine 
Adverse events 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 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. 
7.3.4 Unexpected Adverse Event  
An AE is “unexpected” when its nature (specificity) or severity is not consistent with 
applicable product information, such as safety information provided in the package insert, the 
investigational plan, the Investigator’s Brochure, or the protocol.  
7.3.5 Clinically Significant Laboratory Results 
An abnormal test result usually warrants reporting as an AE in the following situations: 
• 
The test result is associated with clinically significant symptoms or signs and/or; 
• 
The test result requires additional diagnostic testing or medical/surgical intervention 
and/or; 
• 
The test result leads to a change in dosing or discontinuation of study treatment 
and/or; 

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• 
The test results are regarded as clinically significant by the investigator and/or 
medical monitor. 
7.4 
Adverse Event Monitoring and Recording 
7.4.1 Monitoring Procedures 
All AEs will be recorded from the time of signing of the informed consent form (ICF) 
through the Early Discontinuation/Exit Visit, including during dosing hiatus.  
AE may be identified during subject visits or during the review of the subject diary. Each 
occurrence of an AE should be recorded separately (eg, daily abdominal pain). 
All signs and symptoms associated with an AE should be recorded.  
The investigator will treat subjects experiencing AEs appropriately and observe them at 
suitable intervals until their symptoms resolve or their status stabilizes. 
Each AE will be followed from its onset until the event is resolved or medically stable or 
until Early Discontinuation/Exit Visit, whichever occurs first. AEs ongoing at the time that 
IP is discontinued may not be determined to be medically stable until 30 days after the End 
of Treatment Period, in which case additional monitoring after the Early Discontinuation/Exit 
Visit may be required. 
Any new event or experience that was not present at Screening/Baseline or worsening of an 
event present at Screening/Baseline will be reported as an AE. Unchanged, chronic 
conditions are not AEs and should not be recorded on the AE form of the eCRF.  
Each subject will be provided a diary log to record any AEs between study visits. 
Additionally, AEs may be discovered through any of the following 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/medical notes 
Skin prick test reactions are not considered AE unless the reaction, or a complication from 
the procedure, is considered an SAE, as defined in Section 7.3.1.1. 
Food challenge reactions that occur in the clinic are captured on study specific forms and are 
not reported on an AE form (to avoid duplicate reporting) unless the event is considered an 
SAE, as defined below (Section 7.3.1.1).  
• 
As study product is not used in the DBPCFCs, no AEs occurring from Screening 
DBPCFC can be treatment-related (referring to treatment with study product).  
• 
For food challenge reactions that occur at the Exit DBPCFC, it will also usually be 
the case that study product was not the cause of the reaction, as study product is not 

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used in the challenge. There is, however the possibility that dosing with study product 
in the days prior to Exit DBPCFC could contribute to a reaction encountered during 
the challenge. The investigator must determine if dosing with study product in the 
days prior to Exit DBPCFC likely contributed to any observed reaction. If so, the 
investigator should indicate the level of the relatedness, and provide a brief 
explanation as to the manner in which prior dosing with study product was thought to 
be contributory. 
7.4.2 Recording Procedures 
All AEs will be recorded from the time of signing of the ICF through the Early 
Discontinuation/Exit Visit. Recording of these AEs into the eCRF is described below in the 
eCRF completion guidelines. In addition, SAE and AEI will be entered in a respective AE 
form as detailed in the AE form completion guidelines. Completion of appropriate eCRF and 
AE form in summarized in Table 7 below. 
Any event that meets the definition of an SAE (Section 7.3.1.1) will also be reported to the 
drug safety vendor using an SAE report form as described in Section 7.9.1 in addition to 
completing the AE form. 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. In the event of a death, other supporting data (eg, death 
certificate, medical notes) should be included. Medical notes, with subject identifiers 
redacted, can be scanned and attached to the AE form as well.  
Table 7: 
Adverse Event Recording 
Adverse Event Type 
eCRF 
PV Form 
Severity 
Timeline 
F/U 
Serious Adverse Event 
AE 
SAE Form 
< 24 
hours 
Y 
AEI: Anaphylaxis 
Allergy AE 
AEI Form* 
Muraro/EAACI 
< 24 
hours 
Y 
AEI: Allergic Reactions 
AE 
AEI Form* 
CoFAR 
< 24 
hours 
Y 
AEI: Gastrointestinal AE 
resulting in dosing disruption 
AE 
AEI Form* 
NCI-CTAE 
< 24 
hours 
Y 
AEI: Accidental Food 
Allergen Exposure 
Allergy AE 
AEI Form* 
< 24 
hours 
Y 
AEI: AE associated with 
epinephrine use 
Con Meds 
AEI Form* 
< 24 
hours 
Y 
AEI: Severe AE 
AE 
AEI Form* 
< 24 
hours 
Y 
Other: Food Challenge 
FC 
SAE only 
< 24 
hours 
Y 
Other: Pregnancy 
Appropriate visit 
lab form 
Pregnancy 
Form 
NCI-CTAE 
< 24 
hours 
Y 
Other: Non-serious 
AE 
AEI only 
< 7 days 
Y 
* Unless the AEI fulfils the seriousness criteria, in which case an SAE form should be completed. 

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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 at time points defined in the DSMC charter to review 
accruing safety data. The committee will consist of individuals with extensive multicentre 
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 
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 of allergic reactions will be graded according to the definitions 
developed by the CoFAR group (Appendix 4).  
• 
The severity of anaphylactic reactions will be graded according to the EAACI system 
for grading the severity of anaphylactic reactions (Appendix 3).  
• 
The severity of all other AEs will be graded according to the National Cancer 
Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) system. 
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 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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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 General Grade 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.  
7.7 
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. 
7.8 
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. Adverse events 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 subject completes study treatment, whichever comes first. 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 will be 
required. 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 

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• 
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) 
7.8.1 AE Recording Procedures 
AEs are recorded within the electronic data capture (EDC) system as detailed in the CRF 
completion guidelines.   
7.8.2 SAE Recording and Reporting Procedures 
All SAEs will be reported to the sponsor from the time of signing of the ICF through the 
Early Discontinuation/Exit Visit (at least 14 days after the last AR101 dose). If the 
investigator becomes aware of a SAE in a subject treated by him or her with a suspected 
causal relationship to the IP that occurs after the end of the study, the investigator shall 
without undue delay, report it to the sponsor. 
SAEs 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 site investigator will apply his or 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, institutional review board 
(IRB)/ EC, or the sponsor(s) may suspend further trial treatment or procedures at a site. The 
study sponsor(s) and the regulatory health authorities retain the authority to suspend 
additional enrollment and treatments for the entire study as applicable. 
1. Notify the site’s investigator. 
2. 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. Complete and submit an SAE Form in accordance with the SAE completion 
guidelines. 

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4. 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. 
5. In the event of a death, the SAE form must be completed and transmitted along with 
other supporting data (death certificate, medical notes, etc). 
7.9 
Serious Adverse Event Notification 
7.9.1 Notifying the Sponsor 
Study investigators will provide the drug safety vendor with data of all SAEs as defined per 
the protocol on an ongoing basis. 
The drug safety vendor is responsible for notifying the sponsor and will do so simultaneously 
with the reporting to the clinical database. As noted above, this should be within 24 hours of 
site awareness of the event.  
7.9.2 Expedited SAE Reporting to Regulatory Health Authorities  
The 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 
medical monitor.  
The sponsor will expedite the reporting to all concerned investigator(s), the EC, where 
required, and to the regulatory health authorities, including (when applicable) via 
EudraVigilance Clinical Trial Module (EVCTM) in accordance with CT-3, Article 7.4, 
reports of all adverse drug reactions (ADRs) that are both serious and unexpected in 
accordance with ICH E6 5.16.2 and 5.17.1.  
Specifically, the sponsor shall ensure that all relevant information about suspected serious 
unexpected adverse reactions that are fatal or life-threatening are recorded and reported as 
soon as possible to the competent authorities in all the Member States concerned, and to the 
EC no later than 7 days after knowledge by the sponsor of such a case, and that relevant 
follow-up information is subsequently communicated within an additional 8 days. All other 
suspected serious unexpected adverse reactions shall be reported to the appropriate 
regulatory health authorities and to appropriate EC as soon as possible and within a 
maximum of 15 days of first knowledge by the sponsor. In addition, such expedited reports 
will comply with the applicable regulatory requirement(s) and with the ICH E2A Guideline 
for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting 
and ICH E6 5. The sponsor will provide the DSMC and the drug safety vendor with copies of 
any expedited SAE reports submitted to regulatory health authorities. 
The drug safety vendor will provide these expedited reports to the individual site 
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). 

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Finally, the sponsor will submit to the regulatory authorities all safety updates and periodic 
reports, as required by applicable regulatory requirements including ICH E6 5.17.3 and 
ICH E2F. 
7.9.3 Notifying the Data Safety Monitoring Committee 
The drug safety vendor 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 ECs if requested. 
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 drug safety vendor. Information regarding 
these events will be sent to the DSMC if the event is associated with any of the following: 
• 
Fatal ADR; 
• 
An ER visit; 
• 
Hospitalization; 
• 
Three or more doses of epinephrine being given as treatment for the same episode; 
• 
Assessment of the anaphylaxis as severe, as defined in Appendix 3. 
An initial Adverse Event of Interest form containing the information known to the site at the 
time will be transmitted to the drug safety vendor. The drug safety vendor will then relay to 
the sponsor and DSMC the individual anaphylaxis reports as they are obtained. The site will 
supplement the initial Adverse Event of Interest form with additional information pertaining 
to an event as it becomes available and will forward the information to the drug safety 
vendor. 
7.9.4 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 EC in accordance with applicable local 
regulations and guidelines. 
Once a year throughout the clinical trial, the sponsor shall provide the Member States in 
whose territory the clinical trial is being conducted and the EC with a listing of all suspected 
serious adverse reactions that have occurred over this period and a report of the safety of 
subjects. 
7.10 Other Safety Assessments and Precautions 
7.10.1 Physical Examination and Vital Signs 
Physical examinations will be conducted at visits indicated in Appendix 1 Schedule of 
Events. Height and weight will also be recorded at specified visits. Vital signs will be 
measured, including BP, pulse rate, and body temperature. Except where a full, age 
appropriate, physical examination is specifically indicated, a symptom-directed physical 
exam may be performed. 

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7.10.2 Prior and Concomitant Medications 
Prior and concomitant medications will be duly documented in the CRF.  
7.10.3 Pregnancy Testing and Contraception 
7.10.3.1 Pregnancy Testing  
All female subjects of childbearing potential will undergo a serum pregnancy test at 
Screening and then urine pregnancy test at subsequent visits. 
Females of childbearing potential are defined as all women physiologically capable of 
becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes 
intercourse with a male partner and women whose partners have been sterilized by 
vasectomy or other means, UNLESS they meet the following criteria: at least 12 months of 
natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum 
follicle stimulating hormone (FSH) levels > 40 IU/L or at least 6 weeks post-surgical 
bilateral oophorectomy with or without hysterectomy or hysterectomy, OR are using one of 
the methods of highly effective contraception listed in Section 7.10.3.2.  
Although pregnancy itself is not considered an AE or an SAE, if a subject becomes pregnant 
during the course of the study the pregnancy must be reported to the sponsor and the subject 
should be followed to term or until termination.  
7.10.3.2 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. 
OIT, 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, female 
subjects of childbearing potential are required to practice approved and effective birth control 
for the duration of the current study.  
Study personnel are requested to address questions of sexual history and counselling in 
relation to contraception using sensitivity and a patient-centered approach and, if possible, to 
hold discussions regarding sexual history and contraception with adolescent female subjects 
in a private setting. 
Female subjects are to use a highly effective single 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. Acceptable methods of birth control are the following: 

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• 
Combined (oestrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation (oral, intravaginal or transdermal) 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
(oral, injectable or implantable) 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
• 
Sexual abstinence 
7.11 Stopping Rules 
7.11.1 Overall Stopping Rules 
The study will be suspended at any time if a treatment-associated death occurs in a subject on 
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 IP. 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 relevant regulatory agency(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 periodically 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.  
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. 
In the event of early study closure, subjects who complete at least 9 months of study 
treatment and tolerate the 300 mg/d dose for at least 4 weeks may have the Exit DBPCFC 
and complete the study. AR101-treated subjects who tolerate a single highest challenge dose 
of at least 300 mg peanut protein (443 mg cumulative) in the Exit DBPCFC and 
placebo-treated subjects will be eligible to enroll in ARC008. In this situation, AR101-treated 
subjects who complete at least 9 months of study treatment and tolerate 300 mg/d for at least 
4 weeks, but do not tolerate the single challenge dose of 300 mg peanut protein in the 
ARC010 Exit DBPCFC, may enroll in ARC008 if continued treatment is determined to be 
safe per investigator judgment and after discussion with the medical monitor. AR101-treated 
subjects who complete at least 9 months of study treatment but do not tolerate 300 mg/d for 
at least 4 weeks will not have the Exit DBPCFC but may be eligible to enroll in ARC008 if 
continued treatment is determined to be safe per investigator judgment and after discussion 
with the medical monitor.  

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7.11.2 Individual Stopping Rules 
Individuals may stop the study at any time if they experience subjectively intolerable AEs or 
dosing symptoms. They must halt up-dosing and re-start with a reduced dose if more than 
3 days of dosing are missed. Seven or more consecutive days of missed dosing due to 
non-compliance constitutes an individual stopping rule, as does a significant number of 
episodes of missed dosing (ie, 3 or more consecutive days on at least 3 occasions) during the 
Up-dosing Period. Missing 15 or more consecutive days of dosing for any reason also 
constitutes an individual stopping rule. Section 4.3.1 provides additional individual stopping 
rules. 
Occurrence of any of the following will result in the cessation of dosing:  
• 
Failure to accomplish up-dosing of IP after 3 attempts 
• 
Failure to identify a tolerated dose of IP after 3 attempts at dose reduction  
• 
Administration of 3 or more doses of epinephrine for the treatment of any 
dose-related allergic reaction. 
8. 
IMMUNE CELL CHARACTERIZATION 
Humoral (immunoglobulin; antibody) immune assays will be performed at Screening, at the 
300 mg Up-dosing Visit, and at the Exit or Early Discontinuation Visit. The blood samples 
for these serum-based assays can and should be collected with the same blood draw as the 
CBC.  
8.1 
Peanut-Specific Antibody (Immunoglobulin) Assays 
Antigen immunotherapy has been shown to induce antigen-specific humoral responses. 
The balance of isotypic response may play a role in allergen sensitivity (eg, an increase of 
IgG/IgE).  
The blood sample for antibody analysis should be collected with the same blood draw as the 
CBC. Collection of a sample for antibody analysis, like the CBC, is mandatory. 
At each of the specified time points, a sample of serum will be stored for assessment of 
peanut- and peanut component-specific antibody levels (immunoglobulin assays). Total IgE 
and specific IgE and IgG4 will be measured using UniCAP. Peanut-specific IgE and IgG4 
(included in the immunoglobulin assays) will be measured at the Screening, 300 mg 
Up-dosing, Exit, and Early Discontinuation Visits. Additionally, as part of the 
Screening/Baseline immunoglobulin assays, component-resolved (peanut component 
proteins) peanut IgE testing will be performed. The amount of blood to be drawn will be 
determined on the basis of the requirements of the test and individual laboratory protocols, in 
compliance with local regulations. 
9. 
STATISTICAL CONSIDERATIONS 
This section outlines the major statistical consideration for Study ARC010. A comprehensive 
statistical analysis plan (SAP) will be finalized prior to overall study unblinding.  

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Data will be summarized descriptively by treatment arm and overall. The descriptive 
summary for the categorical variables will include counts and percentages. The descriptive 
summary for the continuous variables will include means, medians, standard deviations, and 
minimum and maximum values. 
All data will be listed for all subjects. 
9.1 
Analysis Populations 
The ITT population (ie, the Full Analysis Set) will consist of all randomized subjects who 
received at least 1 dose of randomized study treatment (AR101 or placebo). Subjects will be 
analyzed according to randomized treatment. The ITT population will be used as the primary 
analysis population for all analyses of efficacy endpoints. 
Since only a small number of subjects are expected to be randomized but not treated and due 
to the double-blind nature of the trial, no bias is introduced by excluding these subjects from 
the ITT population. In order to verify this expectation, sensitivity analyses will be performed 
using the randomized population for the primary and key secondary endpoints. 
The Completer population will include all subjects in the ITT population who undergo the 
Exit DBPCFC. 
A Per Protocol (PP) population may be defined for this study. The PP population will be 
a subset of the Completer population, limited to subjects who have no major protocol 
deviations that may influence the desensitization response. Exclusions will be determined by 
blinded review before database lock and overall study unblinding. Subjects will be analyzed 
according to randomized treatment.  
Sensitivity analyses, to be described in full in the SAP, will be performed using the 
Completer population and PP population (the latter if sufficiently different from the 
Completer population). 
The Safety population will consist of all subjects who receive randomized study treatment. 
The Safety population will be used for summaries of safety parameters. Subjects will be 
analyzed according to treatment received.  
9.2 
Study Endpoint Assessment 
9.2.1 Primary Endpoint 
The primary endpoint is the proportion of subjects who achieve desensitization as determined 
by tolerating 1000 mg as a single dose (2043 mg cumulative) of peanut protein (ie, a top 
single challenge dose of 1000 mg) with no more than mild symptoms at the Exit DBPCFC 
(ie, responders). 
An ITT analysis will be performed as the primary efficacy analysis to test for a treatment 
difference in the response rate. All individuals failing to achieve the success definition 
described above will be considered treatment failures, as will subjects who fail to achieve 
and maintain a 300 mg daily dose of IP (escalation failure non-responders). All individuals 

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who drop out of the study or discontinue OIT prior to undergoing the Exit DBPCFC will be 
considered treatment failures (ie, Missing = Failure).  
Fisher’s exact test will be used to test the treatment difference for desensitization and exact 
CIs will be constructed as follows: (1) exact Clopper Pearson confidence limits will be used 
for the binomial proportion and (2) exact unconditional confidence limits based on the score 
statistic will be used for the difference in proportions. 
9.2.2 Secondary Endpoints 
The secondary endpoints are defined in Section 3.8, and a full description of the analyses 
planned for each will be provided in the SAP. A brief description of the planned analyses for 
the key secondary efficacy endpoints and other selected secondary endpoints is provided 
below. 
9.2.2.1 Analysis of Key Secondary Endpoints 
• 
The proportion of subjects who tolerate at least 600 mg as a single dose (1043 mg 
cumulative) of peanut protein with no more than mild symptoms at the Exit 
DBPCFC: The statistical analysis to be conducted for this key secondary endpoint 
will be similar to that used as for the primary endpoint.  
• 
The proportion of subjects who tolerate at least 300 mg as a single dose (443 mg 
cumulative) of peanut protein with no more than mild symptoms at the Exit 
DBPCFC: The statistical analysis to be conducted for this key secondary endpoint 
will be similar to that used as for the primary endpoint. 
• 
The maximum severity of symptoms occurring following ingestion of peanut protein 
during the Exit DBPCFC: The objective of analyzing this key secondary efficacy 
endpoint is to show that subjects from the AR101 group will have less chance of 
developing more severe levels of symptom severity compared to subjects from the 
placebo group. Symptom severity will be recorded at 4 levels: 0-None, 1-Mild, 
2-Moderate, 3-Severe. Symptom severity data will be collected at each challenge 
dose of peanut protein during the Exit DBPCFC – 3 mg, 10 mg, 30 mg, 100 mg, 
300 mg, 600 mg, and 1000 mg; the maximum severity will be used for each subject in 
the analysis.  
The maximum symptom severity observed at any challenge dose in the Exit DBPCFC 
will be used for each subject in the primary analysis of this key secondary endpoint. 
Subjects without an Exit DBPCFC will have their maximum severity during the 
Screening DBPCFC used, which equates to no change from Screening. 
The number and percent of subjects by maximum severity at the Exit DBPCFC will 
be tabulated by treatment arm. The Cochran-Mantel-Haenszel statistic (with equally 
spaced scores) will be used to test for a treatment difference. The mean of the 
numerical values assigned to maximum severity by treatment group will also be 
reported. 
As supportive analyses, the analysis of maximum severity of symptoms during the 
Exit DBPCFC will be repeated for the maximum severity observed in the DBPCFC at 

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any dose up to a maximum challenge of 600 mg. The analysis will be repeated up 
through a maximum challenge of 300 mg, 100 mg, 30 mg, 10 mg, and 3 mg. 
The key secondary efficacy endpoints will be tested in the ITT population in the hierarchical 
order specified above. Each comparison will be evaluated for statistical significance 
(two-sided p < 0.05) only if all of the preceding tests (not including supportive tests) in the 
hierarchy and the primary analysis of the primary endpoint are statistically significant in 
favor of AR101. The ITT population will be used as the primary population for analysis of 
key secondary endpoints. This closed testing procedure maintains the overall Type I error 
rate at 0.05 (EMEA CPMP, 2002; Cook et al, 2008). If any of the preceding tests are not 
significant, the p-value will be displayed for informational purposes only.  
9.2.2.2 Analysis of Other Selected Secondary Endpoints  
If all of the key efficacy secondary endpoints are found to be statistically significant, 
statistical testing of the other secondary efficacy endpoints will continue in the order that 
they are listed in Section 3.8.1.2 according to the same hierarchical closed testing procedure 
used for the key efficacy secondary endpoints. The other secondary endpoints are included in 
the overall hierarchical testing procedure. However, these endpoints are considered 
supportive in nature to the primary and key secondary endpoints.  
Those secondary efficacy endpoints relating to the outcome of the Exit DBPCFC are 
described below. The statistical methods used for testing the remaining secondary efficacy 
endpoints are described in the SAP. 
• 
Maximum dose achieved with no or mild symptoms at Exit DBPCFC: The 
probability estimates for tolerating each challenge dose or higher of the Exit 
DBPCFC will be calculated based on the discrete hazards model in the ITT 
population with terms for treatment group effect and the MTD at the Screening 
DBPCFC (baseline) in the log10 scale (Chinchilli et al, 2005). Following Chinchilli 
for the PRACTALL consensus report, the extreme value hazard function will be used 
for the discrete-time hazard function and the model will be fit with logistic regression 
with the complementary log-log link function. Subjects with no dose eliciting 
response at the 1000 mg single dose (2043 mg cumulative) will be censored at that 
dose. The probability estimates for each dose level will be tabulated by treatment 
group based on least-squares mean estimates from the above model. The values for 
MTD for subjects who do not undergo the Exit DBPCFC will be imputed using the 
maximum doses of peanut protein tolerated in their Screening DBPCFC. The 
treatment effect hazard ratio and its 95% CI and p-value will be based on the Wald 
statistic.  
• 
Change from baseline in MTD of peanut protein at DBPCFC: Analyses of change 
from baseline MTD will be performed using change calculated on the log10 scale. An 
ANCOVA model of change from baseline MTD at Exit DBPCFC (log10 mg) will be 
fit with terms for treatment group and the MTD at baseline (log10 mg). The values for 
MTD for subjects who do not undergo the Exit DBPCFC will be imputed using the 
MTD of peanut protein in their Screening DBPCFC. The baseline adjusted 
least-squares means with 95% CIs by treatment group and for the treatment group 

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difference will be tabulated. The p-value is based on the F-test for treatment group 
effect adjusted for the MTD at baseline (log10 mg). Residuals for ANCOVA will be 
assessed for non-normality using the Shapiro-Wilk test. If significant at the 0.05 
level, then the Wilcoxon rank sum statistic will be used to test for a treatment group 
difference to examine the robustness of the ANCOVA F-test. 
9.2.3 Supportive Analyses of Primary and Secondary Endpoints 
All analyses described in Sections 9.2.1 and 9.2.2 will be repeated in the Completer 
population and PP population (the latter, if sufficiently different). Sensitivity analyses, using 
different methods to handle missing data, will be described in the SAP.  
9.3 
Subject and Demographic Data 
9.3.1 Study Disposition 
The number and percentage of subjects screened, enrolled, randomized, completed and 
discontinued, entered and completed each study period, and in each analysis population will 
be summarized by treatment group and overall. Reasons for discontinuation from the study 
will be summarized by treatment group and overall. Total duration on treatment and total 
duration on study will also be summarized.  
9.3.2 Baseline Characteristics and Demographics 
Summary descriptive statistics for baseline and demographic characteristics will be provided 
for all screened subjects. Demographic data will include age, race, sex, body weight, height, 
and body mass index. Baseline characteristics include total IgE, ps-IgE, ps-IgG4, 
ps-IgE/IgG4 ratio, results from SPT, and MTD of peanut protein at Screening DBPCFC. 
Baseline and demographic characteristics may also be summarized by baseline ps-IgE level 
and by baseline peanut SPT wheal size. 
9.3.3 Use of Medications 
All medications used will be coded using the World Health Organization drug dictionary. 
The number and percentage of subjects receiving concomitant medications or therapies will 
be summarized by treatment group. 
9.4 
Sample Size and Power Calculations 
The sample size for the study, approximately 160 subjects randomized 3:1 (AR101:placebo), 
has sufficient power to detect a treatment effect for the primary efficacy analysis. In Study 
ARC001, the placebo group response rate (95% CI) in the ITT population was 19% (7%, 
39%) and 0% (0%, 13%) at 443 mg and 1043 mg cumulative peanut, respectively. Subjects 
were enrolled in Study ARC001 if at the Screening DBPCFC they expressed DLS at 
≤ 144 mg cumulative peanut protein whereas in Study ARC010 they will be enrolled if they 
express DLS ≤ 443 mg cumulative peanut protein. Extrapolating to Study ARC010, where 
the primary efficacy endpoint is response rate in the ITT population at 2043 mg cumulative 
peanut protein, the placebo response rate is assumed to be at most 15%. With these 
considerations, a sample size of 120 AR101 and 40 placebo subjects and a 15% placebo 
response rate, there is at least 80% power to detect a response rate of 39% or higher in the 

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AR101 group using Fishers exact test with a 0.05 two-sided Type I error rate. Under the 
same assumptions, there is at least 90% power to detect a response rate of at least 43% in the 
AR101 group. 
10. 
IDENTIFICATION AND ACCESS TO SOURCE DATA  
10.1 Electronic Data Capture System 
Data collection will occur via an EDC system to allow easy access to enrollment 24 hours a 
day, 7 days a week. As data are entered, they are validated through range and within-form 
consistency checks. The investigator must ensure that all CRFs are completed in a timely 
fashion for all subjects at his or her site. 
10.2 Certification in the Use of EDC System 
The clinic and laboratory staff will be trained in the use of the data entry 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. 
10.3 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. 
10.4 Access to Data 
The investigational sites shall periodically permit authorized representatives of the Study 
sponsor and/or regulatory health authorities to examine clinical records and other source 
documents for the purpose of safety monitoring, quality assurance reviews, audits, and 
evaluation of the study progress throughout the entire study period. The investigator is 
required by law and applicable guideline (21 CFR 312.62, EU Clinical Trials Directive 
2001/20/EC, and ICH E6) to keep accurate case records for at least 2 years after acceptance 
of a licensure application and record observations to assure the safe conduct of the study, or 
if no application is to be filed or if the application is not approved for such indication, until 
2 years after the investigation is discontinued and Regulatory Authorities are notified, or 
longer if required by local regulation. 
11. 
QUALITY CONTROL AND QUALITY ASSURANCE 
11.1 Statement of Compliance 
This study will be conducted using current Good Clinical Practice (GCP), as delineated in the 
United States CFR – 21 CFR Parts 50, 54, and 312 and in the ICH GCP, national and 
international regulations and directives as appropriate, and according to the criteria specified 
in this study protocol. Before study initiation, the protocol and the informed consent/assent 
documents will be reviewed and approved by an appropriate IRB/EC and the applicable 
regulatory health authority of the country in which Study ARC010 is conducted. Any 
amendments to the protocol must also be approved by the sponsor, DSMC, and IRB/EC and 

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submitted to the applicable regulatory health authorities before they are implemented. Any 
amendments to the consent materials must also be approved by the Aimmune and the 
IRB/EC before they are implemented. 
11.2 Informed Consent/Assent 
The informed consent/assent form is a means of providing information about the study to 
a prospective adult subject or a pediatric subject’s parent/guardian and allows for an 
informed decision about participation in the study. Because the study population will 
comprise only subjects 4 to 17 years of age, parents or legal guardians will be asked to read, 
sign, and date a consent form before a child enters the study, undergoes any study-specific 
procedures, or takes IP. Children will sign an assent as appropriate. Consent materials for 
parents/guardians who do not speak or read English will be translated into the appropriate 
language. The informed consent/assent form will be evaluated for revision whenever the 
protocol is amended or new safety information becomes available. A copy of the informed 
consent/assent will be given to a prospective pediatric subjects’ parent/guardian for review 
and subjects (and parent/guardian) will be allowed as much time as they need to consider 
their participation in the study. Where required by local authorities, both parents must sign 
the consent form before a child can be enrolled in the study. The attending physician will 
review the consent/assent and answer questions, as well as emphasize the need to avoid 
allergen exposure other than to IP, and the necessity to continue exposure to IP to maintain 
de-sensitization. The prospective pediatric subject’s parent/guardian will be told that being in 
the study is voluntary and that he or she may withdraw his/her child from the study at any 
time, for any reason. The subject or subject’s parent/guardian must be given a copy of the 
signed and dated consent/assent form. Written informed consent/assent must be in place prior 
to the commencement of any study-related procedures. 
11.3 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.  
12. 
RESOURCE SHARING 
All data derived from this study will be sent to the Reporting Center for storage and analysis. 
Subject data will be anonymized to maintain subject confidentiality. All-important findings 
derived from these studies will be published in peer-reviewed scientific journals in a timely 
manner. The sponsor will review all manuscripts prior to submission to journals for 
publication and all abstracts prior to submission to national and international meetings. All 
data sets will be archived by the Reporting Center and may be made available to interested, 
outside investigators with the approval by the sponsor.  
13. 
PROTOCOL DEVIATIONS 
The investigators and site staff will conduct the study in accordance with the protocol. Any 
change, divergence, or departure from the study design or procedures constitutes a protocol 
deviation. Whenever applicable, corrective actions will be developed by the site and 
implemented promptly as a result of protocol deviations.  

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13.1 Major Protocol Deviation (Protocol Violation) 
A protocol violation is a deviation from the IRB/EC-approved protocol that may affect the 
subject's rights, safety, or well-being and/or the completeness, accuracy, and reliability of the 
study data. In addition, protocol violations include willful or knowing breaches of human 
subject protection regulations, or policies, any action that is inconsistent with medical and 
ethical principles, and a serious or continuing non-compliance with federal, state, local, or 
institutional human subject protection regulations, policies, or procedures. 
13.2 Non-Major Protocol Deviation 
A non-major protocol deviation is any change, divergence, or departure from the study 
design or procedures of a research protocol that does not have a major impact on the 
subject’s rights, safety, or well-being, or the completeness, accuracy, and reliability of the 
study data.  
13.3 Reporting and Managing Protocol Deviations 
Non-major protocol deviations related to data entry or visit adherence are captured within the 
data system and are not additionally reported on a separate CRF.  
The study site principal investigator has the responsibility to identify, document, and report 
protocol violations/deviations and appropriate corrective and preventative action plans. 
However, protocol violations/deviations may also be identified during site monitoring visits 
or during other forms of study conduct review.  
Where necessary, the investigator can implement a deviation to the protocol in order to 
eliminate an immediate hazard to a study subject, although every effort should be made to 
discuss this with the sponsor’s medical monitor beforehand. Protocol deviations must be 
clearly documented and the reasons for the deviation included with the documentation. In 
cases where protocol deviations lead to the protocol being amended, the amended protocol 
will be submitted to the relevant IRB/IEC and, where required, will also be submitted to the 
relevant regulatory authority.   

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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;124:286-291, 291 e1-
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Report of the Nomenclature Review Committee of the World Allergy Organization, October 
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Appendix 1: Schedule of Events 
Procedure 
SCREEN-
ING 
PERIOD  
(Day -27 
to Day 0) 
INITIAL 
ESCALATION 
PERIODa  
UP-DOSING PERIOD 
20 to 40 Weeks 
Visits Every 2 Weeks (± 3 Days) 
MAINTENANCE 
PERIOD 
12 to 16 Weeksb 
Early DC 
Visitc  
14 to 16 
Days after 
Last Dose 
Exit Visitd 
12 to 16 
Weeks After 
First Dose of 
300 mg/d 
Unscheduled 
Visite 
Day 1 
Day 2 
Up-dosing 
Visits 
80 mg 
Up-dosing 
Visit 
300 mg 
Up-dosing 
Visitc 
Maintenance 
Visits 
 
Informed consent/assentf 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion  
X 
X 
 
 
 
 
 
 
 
 
Review of Subject Eligibility 
Formg 
X 
X 
 
 
 
 
 
 
 
 
Randomize subject 
 
Xh 
 
 
 
 
 
 
 
 
Medical and allergy history  
X 
 
 
 
 
 
 
 
 
 
Diet history (food allergen) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Contraception review 
 
 
 
X 
X 
X 
X 
 
 
X 
Physical examinationi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Spirometry (FEV1) and/or 
PEFRk 
X 
 
X 
 
 
 
 
X 
X 
X 
PEFRl 
 
X 
 
X 
X 
X 
X 
 
 
X 
Asthma assessmentm 
X 
 
 
 
X 
X 
 
X 
X 
X 
FAQLQ & FAIM questionnairen 
X 
 
 
 
 
 
 
X 
X 
 
TSQM-9o 
 
 
 
 
 
 
 
X 
X 
 
Exit questionnaireo 
 
 
 
 
 
 
 
X 
X 
 
Palatability questionsp 
 
 
 
 
 
 
 
X 
X 
 
Serum pregnancy testq 
X 
 
 
 
 
 
 
 
 
 
Urine pregnancy testq 
 
 
 
 
X 
X 
 
X 
X 
X 
Blood draw (CBC/ 
immunology)r 
X 
 
 
 
 
X 
 
X 
X 
X 
Optional additional blood draw 
for exploratory immune cell 
characterizations 
X 
 
 
 
 
X 
 
X 
X 
 
SPT 
X 
 
 
 
 
X 
 
X 
X 
X 

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Procedure 
SCREEN-
ING 
PERIOD  
(Day -27 
to Day 0) 
INITIAL 
ESCALATION 
PERIODa  
UP-DOSING PERIOD 
20 to 40 Weeks 
Visits Every 2 Weeks (± 3 Days) 
MAINTENANCE 
PERIOD 
12 to 16 Weeksb 
Early DC 
Visitc  
14 to 16 
Days after 
Last Dose 
Exit Visitd 
12 to 16 
Weeks After 
First Dose of 
300 mg/d 
Unscheduled 
Visite 
Day 1 
Day 2 
Up-dosing 
Visits 
80 mg 
Up-dosing 
Visit 
300 mg 
Up-dosing 
Visitc 
Maintenance 
Visits 
 
Epinephrine auto-injector checkt 
X 
 
 
 
 
 
 
 
 
 
DBPCFC (2 parts within 7 days) 
Xu 
 
 
 
 
 
 
 
Xv 
 
Peanut / food allergy education 
X 
 
 
 
X 
X 
 
 
 
X 
Reminder to avoid peanut 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
Monitor AEs and allergic 
symptomsw 
Xx 
X 
X 
X 
X 
X 
X 
Xw 
Xw 
X 
Administration of OIT at site 
 
X 
X 
X 
X 
X 
X 
 
 
X 
Dispense / return unused IP 
 
 
Xy 
X 
X 
X 
X 
 
 
X 
Monitor for dosing compliance 
 
 
 
X 
X 
X 
X 
 
 
X 
Home dosing instruction 
 
 
X 
 
X 
X 
Xz 
 
 
X 
Telephone follow-upaa 
 
 
X 
X 
X 
X 
 
 
 
X 
Treatment unblindingbb 
 
 
 
 
 
 
 
 
X 
 
Abbreviations: AEs = adverse events; DBPCFC = double-blind, placebo-controlled food challenge; DC = discontinuation; FAIM = food allergy independent measure; 
FAQLQ = food allergy-related quality of life questionnaire; FEV1 = forced expiratory volume in 1 second; IP = investigational product; Maint, maintenance; OIT = oral 
immunotherapy; PEESS v2.0 = Pediatric Eosinophilic Esophagitis Symptom Scores, version 2.0; PEFR = peak expiratory flow rate; SPT = skin prick test; TSQM-9 = 
Treatment Satisfaction Questionnaire for Medication. 
a) 
Initial Escalation is scheduled within 10 days after the Screening DBPCFC and must occur within 6 weeks of signing the consent/assent form.  
Day 1: Escalation to at least 3 mg or 6 mg, as tolerated (subjects who cannot tolerate 3 mg are escalation failures). Day 2: Confirm tolerance of 3 mg. Day 2 is the next 
consecutive day after Day 1 unless unforeseen circumstances (eg, intercurrent illness) create a safety risk (Section 6.3.2.1). 
b) 
The Maintenance Period lasts for approximately 12 weeks but may be extended up to a maximum of 16 weeks or to a maximum study duration of 56 weeks, whichever is 
shorter (Section 6.3.3.3). There is a ± 3-day visit window for all visits in the Maintenance Period. The first Maintenance Visit is 2 weeks after the 300 mg Up-dosing 
Visit. The next 3 visits are at 6, 10, and 12 weeks after the 300 mg Up-dosing Visit. If at 12 weeks after the 300 mg Up-dosing Visit the subject has maintained a dose of 
300 mg/d for approximately 12 weeks, without the use of symptomatic therapy for the last 4 weeks, the Exit Visit will be performed. If that is not the case, then the 
subject will continue in the study for up to 4 more weeks of 300 mg/d dosing before proceeding to the Exit Visit. 
c) 
Early Discontinuation Visit applies to subjects who fail initial escalation or up-dosing or prematurely discontinue study treatment. 
d) 
Exit Visit applies to subjects who tolerate 300 mg/d and are maintained on this dose for approximately 12 weeks (up to a maximum of 16 weeks).  
e) 
Any or all procedures performed at Up-dosing Visits and spirometry may be performed at Unscheduled Visits.  
f) 
Before any other study procedures. 
g) 
Subject Eligibility Form completed by the site at Screening is reviewed by the medical monitor to confirm whether subject may be randomized, and approval must be 
verified before randomization. 
h) 
Randomization occurs once subject eligibility has been confirmed by the medical monitor (following the medical monitor’s review of the Subject Eligibility Form). 
i) 
Physical examination including height and weight at: Screening, Initial Escalation Day 1 (not height), and the Up-dosing 80 mg and 300 mg, Exit, and Early 
Discontinuation Visits. Symptom-directed physical examination (at investigator’s discretion [ie, not necessarily include height and weight])) at: Initial Escalation Day 2, 
Up-dosing Visits (except the 80 mg and 300 mg Up-dosing Visits), and Maintenance Visits.  

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j) 
Vital signs: blood pressure, pulse rate, and body temperature. Screening, Exit, and Early Discontinuation Visits: Where a DBPCFC occurs at these visits, vital signs are 
measured just before each DBPCFC challenge dose or at 15-20 minutes post-dose, if the between challenge dosing interval is prolonged. Initial Escalation Days 1 and 2: 
pre-dose and post-dose (within 15-30 minutes post-dose, at 30 minutes thereafter, and for the duration of the post-dose observation period). Up-dosing Visits: pre-dose 
and post-dose (within 15-30 minutes post-dose, and at 15-30 minute intervals thereafter for the post-dose observation period). Maintenance Visits: As for Up-dosing 
except post-dose measurements do not need to continue beyond 30 minutes unless the post-dose observation period is extended beyond 30 minutes. 
k) 
Spirometry (FEV1) and/or peak expiratory flow rate (PEFR): conducted prior to the start of the DBPCFC, 3 attempts should be made with the best value recorded. 
PEFR should be measured at the same time of day for each visit assessment (eg, morning, afternoon, evening). 
l) 
PEFR: 3 attempts should be made with the best value recorded. PEFR should be measured at the same time of day for each visit assessment (eg, morning, afternoon, 
evening). If a subject’s pulmonary status is in question at any time during the study, performance of pulmonary function testing (spirometry) is suggested. 
m) 
For subjects with asthma only: evaluation of asthma severity using the 2007 NHLBI Criteria (Appendix 2) and the Asthma Control Test questionnaire.  
n) 
FAQLQ and FAIM questionnaires to be completed prior to the Screening DBPCFC and after completion of the Exit DBPCFC and the subject’s treatment assignment has 
been unblinded. 
o) 
TSQM-9 and Exit questionnaire to be completed after completion of the Exit DBPCFC and the subject’s treatment assignment has been unblinded.  
p) 
Palatability questions to be answered before the Exit DBPCFC.  
q) 
For females of childbearing potential only. To be performed and results obtained prior to DBPCFC, where applicable.  
r) 
Blood draw for IgE and IgG4 is to be drawn prior to DBPCFC.  
s) 
Separate informed consent required. No more than 2.5 mL/kg may be drawn, up to a maximum of 70 mL on any one study day. Multiple attempts to obtain blood, and 
repeat samples can be collected where necessary for damaged samples or safety reasons. 
t) 
It must be verified that the subject has an epinephrine auto-injector prior to the subject leaving the clinic on day 1 of the Screening DBPCFC. 
u) 
At the end of the Screening period, eligible subjects who satisfy all other Screening requirements, will undergo a DBPCFC a maximum challenge dose of 300 mg 
(444 mg cumulative).  
v) 
Subjects who up-dose to 300 mg and maintain this dose for approximately 12 weeks without symptomatic therapy for at least the last 4 weeks will undergo the Exit 
DBPCFC at the end of Maintenance Period to a maximum challenge dose of 1000 mg (2043 mg cumulative).  
w) 
AEs and allergic symptoms will be collected from the point of signing the ICF until 30 days after the subject completes study treatment. Each event should be evaluated 
from the point of onset until the event is resolved or medically stable, or until 30 days after the subject completes study treatment, whichever comes first.  
Subjects with ongoing AEs at early discontinuation or study exit will have safety follow-up for at least 30 days or until the AEs resolve or stabilize, whichever is last 
(Section 4.3.2). Subjects who have gastrointestinal AEs with prolonged disruption of dosing or who discontinue treatment due to gastrointestinal AEs will have safety 
follow-up for 6 months or until the chronic/recurrent gastrointestinal AE resolve or stabilize, whichever is last. These subjects will complete the PEESS v2.0 
questionnaire while symptomatic, at the time of treatment discontinuation, and monthly for 6 months during safety follow-up (Section 7.3.3.2). Subjects may complete 
the PEESS v2.0 at home and send it to the clinic, or at the clinic if they have monthly clinic visits. Subjects who discontinue treatment due to gastrointestinal AEs will be 
asked to return to the clinic for evaluation monthly for at least 6 months (if asymptomatic, telephone follow-up may be appropriate per investigator discretion).  
x) 
Assessment of signs and symptoms of allergic reaction is to be performed at the same time points vital signs are measured during the DBPCFC procedures. 
y) 
The first dose of home dosing study medication (3 mg/d) is taken by the subject on the day following Initial Escalation Day 2 (ie, Day 3). 
z) 
The first visit of the Maintenance Period only. 
aa) 
Phone calls will occur 1 day after Initial Escalation Day 2 and each Up-dosing Visit to inquire about allergic symptoms and promote dosing compliance. 
bb) 
Subject will be unblinded after the Exit DBPCFC is completed, all major data queries are resolved, and the follow-on study ARC008 is available at the study site.  
If ARC008 is not yet available the study site, subjects may continue blinded study treatment and have clinic visits every 4 weeks in ARC010 until ARC008 is available. 
Subjects who complete 12 weeks of maintenance and do not tolerate 300 mg peanut protein at the Exit DBPCFC will not continue blinded study treatment in ARC010.  

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Appendix 2: 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 
Night time 
awakenings 
Lung function 
Interference 
with normal 
activity 
Short acting 
inhaled beta-
agonist use 
Intermittent 
(Step 1) 
≤ 2 days per 
week 
≤ 2 × /month 
Normal FEV1 between 
exacerbations 
FEV1 > 80% predicted 
FEV1/FVC normala 
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 
a Normal FEV1/FVC: 8-19 years = 85% 
 

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Appendix 3: 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 (EAACI - Muraro et al, 2007) is 
fulfilled: 
1. Acute onset of an illness (minutes to hours) with involvement of: 
o Skin/mucosal tissue (eg, generalized hives, itch, or flush, swollen lips/tongue/uvula), 
AND 
o Airway compromise (eg, dyspnea, stridor, wheeze/ bronchospasm, hypoxia, reduced 
PEFR) AND/OR 
o Reduced BP or associated symptoms (eg, hypotonia, syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to the allergen (minute to 
hour): 
o Skin/mucosal tissue (eg, generalized hives, itch/flush, swollen lips/tongue/uvula) 
o Airway compromise (eg, dyspnea, stridor, wheeze/bronchospasm, hypoxia, reduced 
PEFR) 
o Reduced BP or associated symptoms (eg, hypotonia, syncope, incontinence) 
o Persistent GI symptoms (eg, nausea, vomiting, crampy abdominal pain) 
3. Reduced BP after exposure to the allergen (minutes to hours): 
o Infants and children: low systolic BP (age-specific) or > 30% drop in systolic BP. 
Low systolic BP for children is defined as < 70 mmHg from 1 month to 1 year; less 
than (70 mmHg + [2 × 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 Severity Grading (Muraro et al, 2007) 
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 

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Appendix 4: Allergic Reaction Severity Grading 
The CoFAR grading system for allergic reactions is displayed in Table A4.  
Table A4:  
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 
intervention/therapy is 
required. Hospitalization 
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 5: Guidance for Determining When an Episode of Anaphylaxis Should Be 
Reported as a Serious Adverse Event (SAE) 
For an episode of anaphylaxis to be considered an SAE, the sponsor advises that the event satisfy 
1 of the outcome-based definitions of SAE specified in Section 7.3.1.1, with the stipulations 
(denoted in italics) indicated. These stipulations follow from, and are consistent with, the criteria 
for DSMC reporting (Section 7.9.3): 
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 3 and of a Grade 4 allergic reaction, as defined in 
Table A4 of Appendix 4.   
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 of serious event: 
o 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 
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. 
o One or 2 intramuscular injections of epinephrine should ordinarily NOT be construed 
as intensive therapy. 
o 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.