Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization in Children and Adults (PALISADE) Follow-on Study
Phase: PHASE3
Conditions: Peanut Allergy
Sponsor: Aimmune Therapeutics, Inc.

 
 
 
CLINICAL STUDY PROTOCOL 
 
 
 
 
ARC004 
Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization in 
Children and Adults (PALISADE) Follow-On Study 
 
 
 
 
Protocol Amendment 5.0 – 12 Apr 2018 
Reference Numbers:  NCT02993107, EudraCT 2016-004941-94 
 
 
 
 
 
 
 
 
 
 
 
Aimmune Therapeutics, Inc. 
8000 Marina Blvd, Suite 300 
Brisbane, CA  94005 
United States 
 
 
 

CLINICAL STUDY PROTOCOL 
Protocol Title: 
Peanut Allergy Oral Immunotherapy Study of 
AR101 for Desensitization in Children and Adults 
(PALISADE) Follow-on Study 
Investigational Drug: 
AR101, Characterized Peanut Allergen 
Protocol Number: 
ARC004 
IND Number: 
EudraCT Number: 
15463 
2016-004941-94 
Sponsor: 
Aimmune Therapeutics, Inc. 
8000 Marina Boulevard 
Suite 300 
Brisbane, CA 94005 
Current Version/Approval date: Amendment 5.0 (Global) 
12 April 2018 
Previous Versions: 
Amendment 4.0 (Global) 
05 March 2018 
 
Amendment 3.0 (Global) 
12 June 2017 
 
Amendment 2.4 (Germany) 
09 May 2017 
 
Amendment 2.3 (Ireland) 
12 April 2017 
 
Amendment 2.2 (Sweden) 
07 April 2017 
 
Amendment 2.1 
(United Kingdom) 
21 March 2017 
 
Amendment 2.0 (Global) 
07 February 2017 
 
Amendment 1.0 (Global) 
28 October 2016 
 
Original (Global) 
13 September 2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 ARC004 
Sponsor Personnel 
Clinical Lead, Clinical 
Operations 
Jerome Pinkett 
Aimmune Therapeutics, Inc. 
Chief Medical Officer 
Daniel C. Adelman, MD 
Aimmune Therapeutics, Inc. 
Sponsor Medical Monitor 
Kenneth Krantz, MD, PhD 
Aimmune Therapeutics, Inc. 
 

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Principal Investigator Protocol Acknowledgement 
Protocol ARC004 
Version:  Amendment 5.0 (Global) 
Date:  12 Apr 2018 
Sponsor: Aimmune Therapeutics, Inc. 
Short Title:  PALISADE Follow-on Study 
I have read this Clinical Study Protocol. As the Principal Investigator, I agree to 
conduct this protocol according to Good Clinical Practice (GCP), 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 (ICH) “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, state, federal, and 
international requirements. 
 
 
 
 
 
Principal Investigator (Print) 
 
 
 
 
 
 
Principal Investigator (Signature) 
Date 
 
 
 
 
 
 
 
 

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Protocol ARC004 Synopsis 
Title 
Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization  
in Children and Adults (PALISADE) Follow-On Study 
Short Title 
PALISADE FOLLOW-ON STUDY 
Clinical Phase 
3 
IND 
15463 
IND Sponsor 
Aimmune Therapeutics, Inc.  
Number of 
Subjects 
Up to approximately 500 peanut-allergic subjects who complete ARC003 and 
consent to participate in ARC004 will be enrolled. 
Objectives 
The primary objective of this study is to determine the safety, tolerability and 
efficacy of AR101 characterized oral desensitization immunotherapy (CODITTM) 
using alternative maintenance dosing intervals. 
The secondary objectives are: 
• To confirm the safety profile of AR101 as measured by the incidence of 
adverse events (AEs), including serious adverse events (SAEs) 
• To confirm the efficacy of AR101 through reduction in clinical reactivity, 
measured in a double-blind, placebo-controlled food challenge (DBPCFC) to 
a cumulative dose of 4043 mg 
• To evaluate subjects’ quality of life (QoL) and treatment satisfaction during 
AR101 treatment on daily and nondaily treatment regimens 
• To evaluate the long-term immunologic effects of AR101 treatment 
Study Design 
This is an international, multicenter, open-label, 2-arm follow-on study that will 
explore alternate dosing interval regimens during extended maintenance with AR101.  
Group 1 (Placebo Crossovers):  
Subjects who complete the placebo arm of ARC003 are eligible to enroll in ARC004. 
Subjects will enter Group 1 and will undergo initial escalation, up-dosing, and 
maintenance with AR101 as in the active arm of ARC003. The Initial Escalation 
Period consists of a step-wise dose-escalation from 0.5 to 3 or 6 mg (as tolerated) on 
Day 1 and confirmation of the ability to tolerate a single dose of 3 mg on Day 2. The 
Up-dosing Period is 22 to 40 weeks in duration and consists of dose escalations every 
2 weeks up to a maximum of 300 mg/d (as tolerated). The Maintenance Period 
consists of daily dosing at 300 mg/d for approximately 24 weeks, at which point 
Group 1 subjects will undergo a DBPCFC to a maximum cumulative dose of 4043 
mg peanut protein to test the efficacy of AR101 in ARC003 placebo crossovers after 
6 months of daily maintenance. All Group 1 subjects tolerating ≥ 443 mg of 
cumulative peanut protein will be eligible to continue in ARC004, and enter the 
Extended Maintenance (EM) Period, initially consisting of ongoing daily 
maintenance therapy at 300 mg/d. Dependent upon the EM results from ARC004 
Group 2 (below), subjects in Group 1 EM will test the gradual lengthening of their 
dosing interval from daily (QD) to every other day (QOD), twice weekly (BIW), 
once weekly (QW), and finally every other week (QOW), as tolerated. Lengthening 
to each level will occur sequentially (QD then QOD then BIW then QW and finally 
QOW), and only if sufficient evidence exists, based on the analyses of the Group 2 
EM subjects and the ongoing safety of Group 1 subjects, to support progression to 
each level.  
Group 2 (Active Rollovers):  
Subjects who complete the active arm of ARC003 and tolerate a challenge dose of 
≥ 443 mg cumulative of peanut protein at the ARC003 exit food challenge are 
eligible to enroll in ARC004. Group 2 subjects will have undergone the Initial 

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Protocol ARC004 Synopsis 
Title 
Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization  
in Children and Adults (PALISADE) Follow-On Study 
Escalation, Up-dosing, and Initial Maintenance Periods in ARC003 and will therefore 
enter the ARC004 EM period directly, where they will be evaluated in 1 of 3 cohorts 
as outlined below.  
Extended Maintenance: 
The EM periods will differ between and within the 2 groups in duration and dosing 
regimen (see below and Figure 1). All EM subjects who complete their dosing 
regimen, regardless of group or cohort assignment, will have an Exit DBPCFC up to 
a single highest dose of 2000 mg of peanut protein (4043 mg cumulative). ARC004 
will conclude after the last visit for the last subject is completed.  
Group 1 Extended Maintenance: 
Group 1 subjects who tolerate ≥ 443 mg cumulative peanut protein in the 
Post-Maintenance DBPCFC will enter the EM period. Subjects who do not tolerate 
≥ 443 mg cumulative peanut protein are not eligible to continue for safety reasons. 
The EM period for Group 1 subjects will initially consist of QD dosing.  
Conditional upon the safety and DBPCFC outcomes assessed in the Group 2 
participants, Group 1 subjects may have their dosing interval serially lengthened from 
QD to QOD, QOD to BIW, BIW to QW, and QW to QOW, as tolerated. The 
duration of each of these interval extension periods will be adjusted, based on 
Group 2’s experience, from between 8 to 24 weeks, as tolerated. Following the 
completion of their longest tested dosing interval, Group 1 subjects will undergo an 
Exit DBPCFC.  
Group 2 Extended Maintenance:  
Upon entry into the EM phase of the study (Figure 1), Group 2 subjects will be 
consecutively enrolled into cohorts that will conditionally explore alternate dosing 
interval regimens over 28-week study periods, as follows:  
1. EM Cohort 1: The first 120 Group 2 subjects to enter ARC004 will make up 
Cohort 1, and will continue 300 mg of AR101 daily for 28 weeks before 
undergoing an Exit DBPCFC.  
2. EM Cohort 2: The next 50 Group 2 subjects (subjects 121 to 170) enrolling in 
ARC004 will make up Cohort 2 and will take 300 mg of AR101 QOD for 
4 weeks and then BIW (eg, Monday/Thursday) for 24 weeks as tolerated before 
undergoing an Exit DBPCFC.  
3. EM Cohort 3: All remaining Group 2 subjects recruited into ARC004 (subjects 
171 to the end) will make up Cohort 3. This cohort will be randomized 1:1:1 to 1 
of 3 initial strategies:  
a) 300 mg QD for 56 weeks followed by an Exit DBPCFC (Cohort 3A) 
b) 300 mg QD for 28 weeks, then 300 mg QOD for 4 weeks, then BIW for 
24 weeks followed by an Exit DBPCFC (Cohort 3B) 
c) 300 mg QD for 28 weeks, then 300 mg QOD for 4 weeks, then BIW for 
24 weeks, then 300 mg QW for 28 weeks followed by an Exit DBPCFC 
(Cohort 3C) 
Group 2 cohorts will produce evidence during the trial concerning the feasibility and 
safety of adjusting EM dosing from daily to a less frequent schedule. The information 
that becomes available as each cohort proceeds through the study will be evaluated 
before determining whether the next cohort is to advance to a longer interval between 
doses. Lengthening the dosing intervals in subsequent cohorts depends on the safety 
experience of previous cohorts, which will be reviewed by a Safety Monitoring 

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Protocol ARC004 Synopsis 
Title 
Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization  
in Children and Adults (PALISADE) Follow-On Study 
Committee. Individual and cohort stopping rules are discussed further in 
Section 7.8.3.  
End of Participation in ARC004 and Entry into ARC008:  
After the end of participation in ARC004, subjects may enroll in the long-term, 
open-label extension study ARC008 to continue treatment with AR101 at their 
current dosing regimen (QD, BIW, QW, or QOW) or switch to AR101 daily dosing, 
until AR101 becomes commercially available or ARC008 is terminated, as follows: 
• Subjects on any dosing regimen able to tolerate at least the 600 mg single dose 
of peanut protein (≥ 1043 mg cumulative) at their ARC004 Exit DBPCFC will 
continue their current dosing regimen in Treatment Pathway 1 of ARC008 
when that study is available. If ARC008 is not available at the study site, these 
subjects may continue their current dosing regimen and have visits in ARC004 
until they can enroll in ARC008.  
• Subjects who tolerate their nondaily dosing regimen and tolerate at least the 
300 mg single dose of peanut protein (≥ 443 mg cumulative) but are unable to 
tolerate the 600 mg single dose of peanut protein (1043 mg cumulative) at the 
ARC004 Exit DBPCFC will switch to daily dosing with 300 mg AR101 in 
Treatment Pathway 1 of ARC008, per investigator discretion. If ARC008 is not 
available at the study site, these subjects may start AR101 daily dosing and 
have visits in ARC004 until ARC008 is available, then continue dosing in 
ARC008.  
• Subjects on a nondaily dosing regimen who tolerate less than the 300 mg single 
dose of peanut protein (443 mg cumulative) at the Exit DBPCFC may be 
eligible for treatment in ARC008 per investigator judgment and after discussion 
with the medical monitor. If continued treatment with AR101 is determined to 
be safe, these subjects will have the option to receive AR101 daily in Treatment 
Pathway 2 of ARC008, which consists of Repeat Up-dosing (dose escalation 
from 80, 120, or 160 mg to 300 mg daily), Initial Maintenance, and Extended 
Maintenance. If ARC008 is not yet available or able to accept these subjects at 
the study site, these subjects may start AR101 daily dosing and have visits in 
ARC004 until they can enroll in ARC008.  
• Subjects who do not tolerate their nondaily dosing regimen (described in study 
procedures for Extended Maintenance) will have the option to receive AR101 
daily in Treatment Pathway 2 of ARC008, which consists of Repeat Up-dosing 
(dose escalation from 80, 120, or 160 mg to 300 mg daily), Initial Maintenance, 
and Extended Maintenance. If ARC008 is not available at the study site, these 
subjects may start AR101 daily dosing and have visits in ARC004 until 
ARC008 is available, then continue dosing in ARC008.  
• Subjects on a nondaily dosing regimen who miss or withhold their dose for 
> 3 days, including subjects receiving QOD, BIW, or QW dosing who miss or 
withhold their dose for > 14 days, will have the option to receive AR101 daily 
in Treatment Pathway 2 of ARC008, which consists of Repeat Up-dosing (dose 
escalation from 80, 120, or 160 mg to 300 mg daily), Initial Maintenance, and 
Extended Maintenance. If ARC008 is not available at the study site, these 
subjects may start AR101 daily dosing and have visits in ARC004 until they 
can enroll in ARC008.  

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Protocol ARC004 Synopsis 
Title 
Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization  
in Children and Adults (PALISADE) Follow-On Study 
Subjects are not eligible to enroll in ARC008 when continued treatment with AR101 
is determined to be unsafe as follows: 
• Subjects on a daily dosing regimen who are unable to tolerate at least the 
300 mg single dose of peanut protein (443 mg cumulative) at the Exit 
DBPCFC.  
• Subjects not tolerating their nondaily dosing regimen who begin Repeat 
Up-dosing in ARC004, but are unable to dose escalate to AR101 300 mg daily 
and tolerate that dose level for 2 weeks within 26 weeks.  
Inclusion 
Criteria 
1. Completion of ARC003 
2. Written informed consent and/or assent from subjects/guardians as appropriate 
3. Use of effective birth control by female subjects of child-bearing potential 
Exclusion 
Criteria 
1. Early discontinuation from ARC003 
2. Meets any longitudinally applicable ARC003 exclusion criteria (Appendix 7) 
3. (Group 2 only) Failure to tolerate ≥ 443 mg cumulative of peanut protein with no 
or mild symptoms in the ARC003 Exit DBPCFC 
4. Any other condition that, in the opinion of the investigator, precludes 
participation for reasons of safety 
Investigational 
Product and 
Dispensing 
The investigational product is AR101. Doses are expressed as mg of peanut protein. 
For the Initial Escalation and Up-dosing periods, AR101 will be provided in pull-
apart capsules at doses of 0.5, 1.0, 10, 20, and 100 mg. For the Maintenance and EM 
periods, AR101 will be provided in foil-lined sachets at a dose of 300 mg. AR101 
will be shipped directly to investigational sites and will be dispensed according to 
subject identification number, using an interactive response system. Trained 
investigational site personnel will administer AR101 directly or dispense AR101 to 
the subject/ guardian in a manner consistent with the assigned dose level. AR101 is 
administered by QD dosing during Initial Escalation, Up-dosing, and Maintenance, 
and by either QD, QOD, BIW, QW, or QOW dosing during EM.  
Study 
Procedures 
Procedures will be performed as described in the Schedule of Events (Appendix 1).  
Screening: 
Potentially eligible subjects will undergo screening for ARC004 concurrently with 
ARC003 Exit procedures. Subjects who received placebo in ARC003 will be 
screened for Group 1 and subjects who received AR101 in ARC003 will be screened 
for Group 2. 
Initial Escalation (Group 1 only):  
All Initial Escalation doses will be administered by investigational site personnel 
under direct observation. Eligible subjects will initiate treatment with AR101 on 
Day 1, starting at a dose of 0.5 mg increasing the dose at 20 to 30 minute intervals to 
a maximum dose of 6 mg, according to the schedule. Subjects who fail to tolerate the 
3-mg dose on Day 1 will be considered escalation failures and will be discontinued. 
Subjects who tolerate ≥ 3 mg dose on Day 1 will undergo confirmatory dosing of 
a single 3 mg dose on Day 2. Subjects who do not tolerate this confirmatory dose will 
be discontinued. Subjects who tolerate this confirmatory dose will enter the 
Up-dosing Period.  
Up-dosing Period (Group 1 Only)/Repeat Up-dosing (Subjects Switching to 
Daily Dosing): 
Group 1 subjects will receive AR101 starting at a dose of 3 mg once daily and 
escalate, per the Up-dosing Schedule, to 300 mg/d. Subjects who have the option to 

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Protocol ARC004 Synopsis 
Title 
Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization  
in Children and Adults (PALISADE) Follow-On Study 
switch to AR101 daily in AR008 may begin daily dosing and have visits in the 
Repeat Up-dosing Period in ARC004 if ARC008 is not yet available at the study site 
(described in Study Design). These subjects will start at a dose of 80, 120, or 160 mg 
(starting dose at investigator’s discretion) and gradually escalate every 2 weeks to a 
maximum of 300 mg once daily, according to the Repeat Up-dosing Schedule.  
All escalation doses will be administered under direct observation; subsequent doses 
will be dispensed to the subject/guardian and administered at home. Doses may be 
adjusted for tolerability or intercurrent illness; the Up-dosing period may thereby be 
extended from approximately 22 to a maximum of 40 weeks, and the Repeat 
Up-dosing may be up to a maximum of 26 weeks. Subjects unable to escalate to 
300 mg daily within the specified time will be considered escalation failures for 
analysis purposes and exit the study. Group 1 subjects and subjects switching to daily 
dosing able to escalate to 300 mg daily and maintain this dose for 2 weeks will have 
an end of Up-dosing visit/Maintenance visit 1 to enter the Maintenance Period.   
Maintenance Period (Group 1 and Subjects Switching to Daily Dosing):  
Subjects will continue AR101 300 mg once daily, undergoing directly observed 
dosing at Weeks 12 and 24 after entering the Maintenance Period. After 
approximately 24 weeks of daily AR101 treatment at 300 mg as part of the 
Maintenance Period, Group 1 subjects will undergo a Post-Maintenance DBPCFC 
with a maximum dose of 2000 mg of peanut protein (4043 mg cumulative), according 
to the DBPCFC Schedule. Subjects who do not tolerate ≥ 300 mg of peanut protein 
(443 mg cumulative) will be considered treatment failures and will be discontinued. 
Group 1 subjects who tolerate ≥ 300 mg of peanut protein (443 mg cumulative) will 
enter the EM period and continue taking 300 mg of AR101 daily until the results of 
the alternate regimens explored in Group 2 subjects are known.  
Extended Maintenance Period (All Subjects): 
Group 1 subjects who tolerate ≥ 443 mg cumulative peanut protein in the 
Post-Maintenance DBPCFC will enter EM. Subjects who do not tolerate ≥ 443 mg 
are not eligible to continue for safety reasons. The EM period for Group 1 subjects 
will initially consist of QD dosing while the first 3 Group 2 cohorts are undergoing 
evaluation as outlined below. Conditional upon the safety and DBPCFC outcomes 
assessed in the Group 2 participants, Group 1 subjects may have their dosing interval 
serially lengthened from QD to QOD, QOD to BIW, BIW to QW, and QW to QOW, 
as tolerated. The duration of each of these interval extension periods will be adjusted, 
based on Group 2’s experience, from between 8 to 24 weeks, as tolerated. Following 
the completion of the longest tested dosing interval, Group 1 subjects will undergo an 
Exit DBPCFC and ARC004 will conclude.   
Group 2 will consist of 3 cohorts that will each explore a different dose strategy. 
Eligible Group 2 subjects will be consecutively enrolled into 1 of 3 cohorts as they 
exit ARC003 and enter the ARC004 EM period directly. Cohort 1 will consist of the 
first 120 subjects to enter ARC004, and will continue to receive AR101 300 mg on a 
QD schedule.  
The next 50 Group 2 subjects to enter ARC004 will form Cohort 2 and be assigned to 
receive AR101 300 mg QOD for 4 weeks and then BIW (eg, Monday/Thursday) for 
24 weeks, as tolerated. Cohorts 1 and 2 will undergo an EM Week 28 Exit DBPCFC 
to a maximum of 2000 mg (4043 mg cumulative) of peanut protein.  

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All remaining Group 2 subjects will enter Cohort 3 in ARC004 EM and will be 
randomized in a 1:1:1 ratio to ongoing treatment with AR101. 
• Cohort 3A: QD for 56 weeks 
• Cohort 3B: QD for 28 weeks followed by QOD for 4 weeks and then BIW for 
24 weeks, as tolerated 
• Cohort 3C:  QD for 28 weeks followed by QOD for 4 weeks and BIW for 
24 weeks, and finally QW for 28 weeks, as tolerated. 
At the end of each treatment period, qualifying subjects will undergo a maximum 
4043 mg cumulative Exit DBPCFC and complete participation in ARC004.  
The Exit Visit will complete subject participation in ARC004 with one exception:  If 
a study site has not yet received approval for ARC008, subjects will receive 
additional AR101 and will continue dosing and visits in ARC004 until ARC008 is 
able to accept these subjects at the study site.  Subjects will return to the study site for 
an unscheduled visit every 14 weeks to receive AR101 sachets for dosing at home 
and to ensure subject safety.  
Throughout ARC004 EM, the first 2 doses at extended dosing intervals (BIW, QW, 
and QOW) will be administered under direct supervision in the clinic; QOD doses 
may be initiated at home. Thereafter, the doses will be administered at home as 
tolerated, and recorded in the subject diary. Investigators may, at their discretion, 
bring subjects back to the research unit for an observed dose at any time. All AR101 
doses will be judged by the investigator to be tolerated or not tolerated according to 
criteria previously established in ARC003 and specified in Section 6.5.2.  
Any subject receiving nondaily dosing (QOD, BIW, QW, or QOW) who has 1 related 
SAE; 1 related AE graded severe; 2 related AEs occurring on separate occasions, 
both graded moderate; or 3 consecutive doses judged “not tolerated” will be 
considered a treatment failure in the statistical analysis of each cohort and 
discontinued from ARC004 for safety reasons. Such subjects may be eligible to 
enroll in ARC008 on a QD regimen.  If a site has not yet received approval for 
enrollment of subjects into ARC008, the subject will begin daily dosing and have 
visits in the Repeat Up-dosing period in ARC004.  Once the subject reaches the 
target dose of 300 mg daily and maintains this dose for 2 weeks, that subject will be 
able to continue this dosing regimen and enroll in ARC008 when available. 
Early discontinuations due to related AEs, and subjects unable to tolerate a 
prespecified amount (either ≥ 443 mg or ≥ 1043 mg of cumulative) peanut protein 
during the Exit DBPCFC, will be considered failures. If failures affect greater than 
50% of any cohort, then prolongation of the dosing interval in any subsequent cohort 
will cease, and the remaining subjects will be administered AR101 300 mg at the 
longest dosing interval tolerated by a previous cohort (Section 7.8.3).  
Early Discontinuations: 
Subjects who are discontinued for an AE will have that AE evaluated from the onset 
until the event is resolved or medically stable, or for 30 days after the Early 
Discontinuation Visit, whichever comes first. 
Subjects who are discontinued for reasons other than an AE and who do not enter 
ARC008 will be followed for safety for 30 days after the last dose of AR101, 
2 weeks after the last food challenge, or until resolution or stabilization of all AEs 
ongoing at the time dosing is stopped, whichever is longer.  
In addition, subjects who are discontinued from further. AR101 dosing due to chronic 
or recurrent gastrointestinal (GI) AEs will be followed monthly for a minimum of 
6 months, or until resolution or stabilization of all GI AEs.  
For subjects who do not tolerate their nondaily dosing regimen and subjects who 
switch to daily dosing after missing their nondaily dose for > 3 days, the exit 

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Protocol ARC004 Synopsis 
Title 
Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization  
in Children and Adults (PALISADE) Follow-On Study 
DBPCFC will be omitted before discontinuation from ARC004 and enrollment in 
ARC008.  
Subjects who are discontinued will not be replaced. 
Study 
Endpoints 
The primary endpoint is the frequency of treatment-related AEs, including SAEs, 
during the overall study period (from enrollment to the end of EM period). 
Secondary endpoints include: 
• Frequency of anaphylaxis 
• Frequency of use of epinephrine as a rescue medication 
• Frequency of AEs leading to withdrawal of AR101 
• Frequency of AEs in each treatment regimen leading to discontinuation of 
extended interval dosing 
• Frequency of GI AEs of interest (GI AEIs) 
• Frequency of accidental food allergen exposure 
• In subjects with asthma, change in asthma control using the Asthma Control 
Test questionnaire see Appendix 2 
• Frequency of all above safety endpoints by treatment period 
• The proportion of subjects in each regimen tolerating ≥ 1043 mg cumulative of 
peanut protein during their EM Exit DBPCFC  
• The proportion of subjects in each regimen who tolerate ≥ 443 mg cumulative 
of peanut protein during their EM Exit DBPCFC 
• The proportion of subjects in each regimen who tolerate 4043 mg cumulative of 
peanut protein during their EM Exit DBPCFC 
• Maximum tolerated dose and change from baseline* at Post-Maintenance** 
and each EM Exit DBPCFC  
• Maximum severity of symptoms at each challenge dose at Post-Maintenance** 
and each EM Exit DBPCFC 
• Frequency of use of epinephrine as a rescue medication at the 
Post-Maintenance** and each EM Exit DBPCFC 
• Change in QoL as assessed by the food allergy related quality of life 
questionnaire (FAQLQ) and the food allergy independent measure (FAIM) 
questionnaire 
• Satisfaction with AR101 treatment as assessed by the Treatment Satisfaction 
Questionnaire for Medication Version 9 (TSMQ-9) questionnaire and 
additional questions 
• Changes in peanut-specific serum IgE and IgG4 levels 
• Changes in peanut skin prick test (SPT) wheal diameter 
*Baseline is defined as the Screening DBPCFC from ARC003 for both treatment 
groups.  
**Post-Maintenance is defined as the ARC003 Exit DBPCFCs for Group 2. 
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 
• Medical/allergy history  
• Concomitant medications 

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Protocol ARC004 Synopsis 
Title 
Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization  
in Children and Adults (PALISADE) Follow-On Study 
• Physical examination, including height and weight 
• Vital signs (blood pressure [BP], pulse rate [PR], 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 (e.g., active 
wheeze on physical examination) 
• Pregnancy test 
• Diet (food allergen) history 
• Blood draw for peanut-specific IgE and IgG4 (including determination of 
peanut component proteins) (immunoglobulin assays) 
• Complete blood cell count (CBC), obtained with the same venipuncture as the 
blood draw for the immunoglobulin assays 
• Additional blood samples for optional exploratory immunologic studies. These 
can be obtained at selected centers with the same venipuncture as the blood 
draw for the immunoglobulin assays (separate informed consent required). 
• Optional collection of saliva samples for exploratory biomarker development at 
selected centers (separate informed consent required) 
• Skin prick test (SPT) 
• Double-blinded, placebo-controlled food challenges carried out in accordance 
with PRACTALL guidelines per the schedule  
• Clinical research center investigational product administration 
• Dispensing of investigational products for home dosing/return of unused 
investigational products 
• Monitoring for dosing compliance 
• Adverse event (AE) monitoring 
• Assessment of asthma control using the Asthma Control Test questionnaire and 
frequency of asthma rescue medication use in subjects with asthma 
• Change in QoL as assessed by FAQLQ and FAIM questionnaires 
• Satisfaction with AR101 treatment as assessed by the TSMQ-9 questionnaire 
and additional questions 
Statistical 
Considerations 
Because enrollment in this study depends upon completion of Study ARC003, sample 
size will be determined by subject interest in continuing to receive AR101. The 
sample size for ARC004 is thus based on that of ARC003, which had a target N of 
500 and a 3:1 AR101: placebo randomization ratio, providing 89% power to rule out 
a treatment difference (AR101 minus placebo) of 15% or less at the primary endpoint 
of the proportion of subjects who tolerate ≥ 1043 mg cumulative of peanut protein 
with no more than mild symptoms at the Exit DBPCFC. Accrual of 80% of the total 
ARC003 sample into ARC004 would provide an 80% probability of observing 
≥ 1 AE when the background rate of the AE is 4 per 1,000 subjects. No prospective 
power calculation for efficacy has been made in ARC004. 
Data will be summarized using descriptive statistics within treatment group and 
cohort. No specific hypothesis testing or comparisons between the treatment groups 
is planned for this study. Further details on the analytical approach and exploratory 
comparisons across cohorts will be provided in the statistical analysis plan (SAP). 
 

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Initial Escalation Schedule (Group 1 only) 
Day 1 
Dose Number 
AR101 Dose, mg 
Cumulative AR101 Dose, mg 
1 
0.5 
0.5 
2 
1 
1.5 
3 
1.5 
3 
4 
3 
6 
5 
6 
12 
Day 2 
Dose Number 
AR101 Dose, mg 
Cumulative AR101 Dose, mg 
1 
3 
3 
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. 
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. 
 
Up-dosing and Maintenance Schedule (Group 1 only) 
Dose Number 
AR101 Dose, mg 
Interval 
(weeks) 
Percent Increase 
from Previous Dose 
1 
3 
2* 
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 
2 
25 
*Interval includes Day 2 of Initial Escalation. 

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Repeat Up-dosing Schedule 
(Subjects Switching to Daily Dosing) 
Investigational Product Dose, mga 
Interval (weeks) 
80 
2 
120 
2 
160 
2 
200 
2 
240 
2 
300 
2 
a 
All mg doses shown refer to milligrams of peanut protein. 
 
DBPCFC Schedule 
(Post-Maintenance: Group 1 only; Post-Extended Maintenance: Groups 1 and 2) 
Challenge Dose, mg 
Cumulative Dose, mg 
3 
3 
10 
13 
30 
43 
100 
143 
300 
443 
600 
1043 
1000 
2043 
2000 
4043 
 

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Figure 1: Study Schematic 
 
Diamonds represent DBPCFCs; all challenges in ARC004 will be to a total of 4043 mg cumulative peanut protein, according to the table above.  
The initial ARC004 DBPCFC for Group 1 will be completed after approximately 24-week maintenance period 
QD = daily, QOD = every other day, BIW = twice weekly, QW = once weekly, QOW = every other week 
NOTE: The BIW interval begins with 4 weeks of QOD dosing before transitioning to 24 weeks of BIW dosing, as tolerated 
Group 1: Total duration varies, ranging from approximately 88 to 136 weeks 
Group 2, Cohort 1: 28 weeks 
Group 2, Cohort 2: 28 weeks 
Group 2, Cohort 3A: 56 weeks 
Group 2, Cohort 3B: 56 weeks 
Group 2, Cohort 3C: 84 weeks 
 

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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ............................................................................................................................ 19 
1 BACKGROUND AND RATIONALE ........................................................................................................ 21 
1.1 Background ............................................................................................................................................ 21 
1.2 Clinical Trials of AR101 ........................................................................................................................ 22 
1.2.1 ARC001 ...................................................................................................................................... 22 
1.2.2 ARC002 ...................................................................................................................................... 23 
1.2.3 ARC003 ...................................................................................................................................... 23 
1.3 Rationale for the Current Study ............................................................................................................. 24 
1.4 Known and Potential Risks and Benefits of AR101............................................................................... 25 
1.4.1 Risks ........................................................................................................................................... 25 
1.4.2 Benefits ....................................................................................................................................... 26 
2 OBJECTIVES ............................................................................................................................................... 26 
2.1 Primary Objective .................................................................................................................................. 26 
2.2 Secondary Objectives ............................................................................................................................. 27 
3 STUDY DESIGN .......................................................................................................................................... 27 
3.1 Study Periods ......................................................................................................................................... 29 
3.1.1 Initial Escalation (Group 1 Only) ............................................................................................... 30 
3.1.2 Up-dosing (Group 1 Only) .......................................................................................................... 30 
3.1.3 Repeat Up-dosing (Subjects Switching to Daily Dosing) ........................................................... 31 
3.1.4 Maintenance ................................................................................................................................ 32 
3.1.5 Extended Maintenance ................................................................................................................ 33 
4 SELECTION AND WITHDRAWAL OF SUBJECTS ............................................................................. 35 
4.1 Inclusion Criteria .................................................................................................................................... 35 
4.2 Exclusion Criteria................................................................................................................................... 35 
4.3 Early Termination .................................................................................................................................. 36 
4.3.1 Criteria for Early Termination .................................................................................................... 36 
4.3.2 Follow-up of Subjects ................................................................................................................. 37 
4.3.3 Subject Replacement .................................................................................................................. 37 
5 STUDY TREATMENT ................................................................................................................................ 37 
5.1 Formulation, Packaging, and Labeling ................................................................................................... 37 
5.2 Preparation, Administration, and Dosage ............................................................................................... 38 
5.3 Drug Accountability ............................................................................................................................... 39 
5.4 Assessment of Compliance with Study Treatment and Monitoring ....................................................... 40 
5.5 Modification of Study Treatment ........................................................................................................... 40 
5.6 Concomitant Medications ...................................................................................................................... 40 
5.7 Prophylactic Medications ....................................................................................................................... 40 
5.8 Rescue Medications ............................................................................................................................... 40 
5.9 Symptomatic Treatment for Chronic and/or Recurrent Adverse Events ................................................ 41 
5.10 Prohibited Medications .......................................................................................................................... 41 
6 STUDY PROCEDURES .............................................................................................................................. 42 
6.1 Enrollment and Randomization .............................................................................................................. 42 
6.2 Screening and Baseline Visit – (Group 1 and Group 2) ......................................................................... 42 
6.3 Study Visits ............................................................................................................................................ 44 
6.3.1 Initial Escalation: Day 1 (Group 1) ............................................................................................. 44 
6.3.2 Initial Escalation: Day 2 (Group 1) ............................................................................................. 46 

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6.3.3 Up-dosing/Repeat Up-dosing Visits (Group 1 and Subjects Switching to Daily Dosing) .......... 48 
6.3.3.1 Group 1 Up-dosing ....................................................................................................... 48 
6.3.3.2 Repeat Up-dosing (Subjects Switching to Daily Dosing)............................................. 50 
6.3.4 80 mg Up-dosing Visit ................................................................................................................ 50 
6.3.5 End of Up-dosing Visit/Start of Maintenance (Group 1 and Subjects Switching to Daily 
Dosing) ....................................................................................................................................... 51 
6.3.6 Maintenance Visits (Group 1 and Subjects Switching to Daily Dosing) .................................... 52 
6.3.7 Double-Blind, Placebo-Controlled Food Challenge (Groups 1 and 2) ....................................... 54 
6.3.8 All Subjects (Groups 1 and 2): Extended Maintenance Visits .................................................... 54 
6.3.8.1 Alternate Dosing Initiation Visit: Day 1 ....................................................................... 55 
6.3.8.2 Alternate Dosing Initiation Visit: Day 2 ....................................................................... 56 
6.3.9 Follow-up Extended Maintenance Visits .................................................................................... 56 
6.3.10 Exit Visit/Early Discontinuation Visit ........................................................................................ 58 
6.4 Unscheduled Visits / Unscheduled Blood Draws ................................................................................... 60 
6.5 Assessment and Treatment of Allergic Reactions to Peanut OIT .......................................................... 60 
6.5.1 Assessment of the Severity of Acute Allergic Reactions to Peanut OIT .................................... 60 
6.5.2 Assessment of the Tolerability of an Individual Dose of Study Product .................................... 61 
6.5.3 Assessment of the Tolerability of a Dose Level ......................................................................... 63 
6.5.3.1 Assessment of Acute Symptoms Occurring After Dosing ........................................... 63 
6.5.3.2 Assessment of Chronic/Recurrent Symptoms .............................................................. 64 
6.5.4 Treatment of Acute Reactions to Peanut OIT during Initial Escalation (Group 1) ..................... 64 
6.5.5 Treatment for Reactions During the Up-dosing Period (Group 1): Dose Adjustment ................ 67 
6.5.5.1 Reactions to In-Clinic Dosing (Group 1) ...................................................................... 68 
6.5.5.2 Reactions to Dosing at Home (Groups 1 and 2) ........................................................... 71 
6.5.5.3 Dose Adjustment in Response to Intercurrent Adverse Events (QD Regimens only) .. 72 
6.5.6 Treatment for Reactions During the Up-dosing Period: Pharmacological and Supportive 
Treatments .................................................................................................................................. 74 
6.5.7 Reactions Occurring During the Maintenance and Extended Maintenance Periods (Groups 1 
and 2) .......................................................................................................................................... 76 
6.6 Missed Peanut OIT (Study Product) Doses during Up-dosing (Group 1) .............................................. 78 
6.7 Skin Prick Test ....................................................................................................................................... 80 
6.8 Visit Windows ........................................................................................................................................ 80 
6.9 Other Safety Assessments ...................................................................................................................... 80 
6.9.1 Physical Examination and Vital Signs ........................................................................................ 80 
6.9.2 Prior and Concomitant Medications ........................................................................................... 80 
6.9.3 Pregnancy Test............................................................................................................................ 80 
7 SAFETY MONITORING ............................................................................................................................ 81 
7.1 Definitions .............................................................................................................................................. 81 
7.2 Dosing Symptoms as Adverse Events .................................................................................................... 82 
7.3 Definitions of Safety Events .................................................................................................................. 82 
7.3.1 Adverse Event (AE) or Medical Event ....................................................................................... 82 
7.3.2 Serious Adverse Events (SAE) ................................................................................................... 82 
7.3.3 Adverse Events of Interest .......................................................................................................... 83 
7.3.3.1 Anaphylaxis Events ...................................................................................................... 83 
7.3.3.2 Gastrointestinal Adverse Events Resulting in Prolonged Disruption of Dosing .......... 83 
7.3.3.3 Accidental Food Allergen Exposures ........................................................................... 85 
7.3.3.4 Adverse Events Featuring a Severe Symptom .............................................................. 85 
7.3.3.5 Adverse Events Associated with Use of Epinephrine .................................................. 85 

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7.4 Severity Grading .................................................................................................................................... 86 
7.4.1 Guidelines for Determining Causality of an Adverse Event ....................................................... 87 
7.5 Adverse Event Collection Procedures .................................................................................................... 87 
7.5.1 Recording and Reporting Procedures ......................................................................................... 87 
7.5.2 Serious Adverse Event Recording and Reporting Procedures .................................................... 87 
7.6 Serious Adverse Event Notification ....................................................................................................... 89 
7.6.1 Notifying the Sponsor ................................................................................................................. 89 
7.6.2 Expedited SAEs Reporting to Regulatory Health Authorities .................................................... 89 
7.6.3 Other Events Reportable to the Sponsor ..................................................................................... 89 
7.6.4 Review Board and Ethics Committee ......................................................................................... 90 
7.7 Other Safety Assessments and Precautions ............................................................................................ 90 
7.7.1 Physical Examination and Vital Signs ........................................................................................ 90 
7.7.2 Prior and Concomitant Medications ........................................................................................... 90 
7.7.3 Pregnancy Testing and Contraception ........................................................................................ 90 
7.7.3.1 Pregnancy Testing ........................................................................................................ 90 
7.7.3.2 Contraception ............................................................................................................... 90 
7.8 Stopping Rules ....................................................................................................................................... 91 
7.8.1 Overall Stopping Rules ............................................................................................................... 91 
7.8.2 Individual Stopping Rules .......................................................................................................... 92 
7.8.3 Cohort Stopping Rules ................................................................................................................ 93 
8 OPTIONAL MECHANISTIC STUDIES ................................................................................................... 94 
9 STATISTICAL CONSIDERATIONS ........................................................................................................ 94 
9.1 Analysis Populations .............................................................................................................................. 95 
9.2 Study Endpoints ..................................................................................................................................... 95 
9.2.1 Primary Endpoint ........................................................................................................................ 95 
9.2.2 Secondary Endpoints .................................................................................................................. 95 
9.3 Subject and Demographic Data .............................................................................................................. 96 
9.3.1 Baseline Characteristics and Demographics ............................................................................... 96 
9.3.2 Use of Medications ..................................................................................................................... 96 
9.3.3 Study Disposition........................................................................................................................ 96 
9.3.4 Adverse Events ........................................................................................................................... 96 
9.4 Sample Size and Power Calculations ..................................................................................................... 97 
10 IDENTIFICATION AND ACCESS TO SOURCE DATA ....................................................................... 97 
10.1 Web-Based Data Collection and Management System .......................................................................... 97 
10.2 Certification in the Use of Web-Based Data Entry System .................................................................... 97 
10.3 Data Management .................................................................................................................................. 97 
10.4 Access to Data ........................................................................................................................................ 98 
11 QUALITY CONTROL AND QUALITY ASSURANCE .......................................................................... 98 
11.1 Statement of Compliance ....................................................................................................................... 98 
11.2 Informed Consent/Assent ....................................................................................................................... 98 
11.3 Privacy and Confidentiality .................................................................................................................... 99 
12 RESOURCE SHARING............................................................................................................................... 99 
13 PROTOCOL DEVIATIONS ....................................................................................................................... 99 
13.1 Reporting and Managing Protocol Deviations ....................................................................................... 99 
14 REFERENCE LIST .................................................................................................................................... 101 
 

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LIST OF TABLES 
Table 1: 
Initial Escalation Schedule (Group 1 Subjects Only) .................................................................... 30 
Table 2: 
Up-dosing Maintenance Schedule (Group 1 Subjects Only) ......................................................... 31 
Table 3: 
Repeat Up-dosing Schedule (Subjects Switching to Daily Dosing) .............................................. 32 
Table 4: 
DBPCFC Schedule (All Time Points) ........................................................................................... 33 
Table 5: 
Allergy Symptom Severity and Study Product Dose Tolerability ................................................. 62 
Table 6: 
Treatment(s) for Reactions during the Up-dosing Period by Severity of Reaction ....................... 74 
Table 7: 
Procedure(s) Following Treatment of a Reaction Experienced during the Up-dosing Period ....... 75 
Table 8: 
Dosing Guidelines Following Treatment for Reactions Experienced by Subjects in 
Groups 1 and 2 Receiving AR101 at 300 mg QD, QOD, BIW, QW, or QOW During 
Maintenance and Extended Maintenance ...................................................................................... 76 
 
LIST OF FIGURES 
Figure 1: 
Study Schematic ............................................................................................................................ 14 
Figure 2: 
Schematic for Management of Symptoms Occurring During Initial Escalation Day 1 ................. 65 
Figure 3: 
Schematic for Management of Dose Adjustments due to Poorly Tolerated Doses 
(Groups 1 and 2) ............................................................................................................................ 69 
Figure 4: 
Schematic for Temporary Dose Reductions due to Intercurrent Adverse Events (QD 
Regimens Only) ............................................................................................................................. 73 
Figure 5: 
Procedures Following Missed Consecutive Doses of Peanut OIT ................................................. 78 
Figure 6: 
Procedures for Doses Withheld for 8 to 14 Days During the Maintenance Period........................ 79 
Figure 7: 
Reporting Decisions for Adverse Events ....................................................................................... 88 
 
LIST OF APPENDICES 
Appendix 1: Schedules of Events ..................................................................................................................... 103 
Appendix 2: Evaluation of Asthma .................................................................................................................. 125 
Appendix 3: Criteria for Suspected Diagnosis and Severity Grading of Anaphylaxis Criteria for 
Suspected Diagnosis .................................................................................................................... 126 
Appendix 4: Allergic Reaction Severity Grading ............................................................................................. 127 
Appendix 5: Guidance for Determining When an Episode of Anaphylaxis Should Be Reported as a 
Serious Adverse Event ................................................................................................................. 128 
Appendix 6: Exploratory Biochemical and Molecular Substudy of Peanut-Allergic Children and Adults 
with Oral Immunotherapy-related Gastrointestinal Symptoms in Study ARC004 ...................... 129 
Appendix 7: Longitudinally Applicable Exclusion Criteria ............................................................................. 138 

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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ACE 
angiotensin-converting enzyme inhibitors 
ACT 
Asthma Control Test 
AE 
adverse event 
AEI 
adverse event of interest 
AR101 
characterized peanut allergen 
ARB 
angiotensin-receptor blocker 
BA/BE 
bioavailability/bioequivalence 
BIW 
twice weekly 
BP 
blood pressure 
CBC 
complete blood cell count 
CFR 
US Code of Federal Regulations 
CODIT™ 
Characterized Oral Desensitization Immunotherapy™ 
CoFAR 
Consortium of Food Allergy Research 
CRC 
clinical research center 
CRF 
case report form 
DBPCFC 
Double-Blind, Placebo-Controlled Food Challenge 
EAACI 
European Academy of Allergy & Clinical Immunology 
EC 
ethics committee 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EGD 
esophagogastroduodenoscopy 
ELISA 
enzyme-linked immunosorbent assay 
EM 
extended maintenance 
EoE 
eosinophilic esophagitis 
FAIM 
food allergy independent measure 
FAQLQ 
food allergy related quality of life questionnaire 
FDA 
US Food and Drug Administration 
FEV1 
forced expiratory volume in 1 second (spirometry) 
GCP / cGCP 
Good Clinical Practice / Current Good Clinical Practice 
GI 
gastrointestinal 
HPLC 
high-performance liquid chromatography 
ICS 
inhaled corticosteroids 
ICH 
International Council for Harmonisation 
ICON 
International consensus on anaphylaxis 
IgE 
immunoglobulin E 
IgG 
immunoglobulin G 
IM 
intramuscular 
IND 
Investigational New Drug (application)  
IRB 
institutional review board 
ITT 
intent-to-treat 
IV 
intravenous 
IXRS 
Interactive web-based response system 

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Abbreviation 
Definition 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NHLBI 
National Heart, Lung, and Blood Institute 
OFC 
oral food challenge 
OIT 
oral immunotherapy 
PEESS 
Pediatric Eosinophilic Esophagitis Symptom Scores 
PEFR 
peak expiratory flow rate 
PR 
pulse rate 
PRACTALL 
PRACTical issues in ALLergology Joint United States/European Union Initiative 
QD 
once daily 
QOD 
every other day 
QoL 
quality of life 
QOW 
every other week 
qPCR 
quantitative polymerase chain reaction 
QW 
once weekly 
REB 
research ethics board 
SAE 
serious adverse event 
SAP  
statistical analysis plan 
SCIT 
subcutaneous immunotherapy 
SMC 
Safety Monitoring Committee 
SPT 
skin prick test 
SUSAR 
suspected unexpected serious adverse reaction 
SVM 
support vector machine 
TEAE 
treatment-emergent adverse event 
TSQM-9 
Treatment Satisfaction Questionnaire for Medication Version 9 
WHO 
World Health Organization 

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1 BACKGROUND AND RATIONALE 
1.1 
Background 
Peanut allergy is a common and serious condition that disproportionately affects children and 
is associated with severe reactions, including life-threatening anaphylaxis. Furthermore, the 
prevalence of peanut allergy, like other food allergies, has been rising, and is now at high 
levels, affecting up to 1.5% of the population (Branum et al, 2008; Sicherer and Sampson, 
2014). The current standard of care in management of peanut allergy is a peanut-avoidant 
diet, along with education of the patient and family in the acute management of an allergic 
reaction, including ready access to self-injectable epinephrine. The burden of avoidance and 
the constant fear of accidental exposure negatively affect the health-related quality of life 
(QoL) for 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, 2014). 
In addition, peanut-avoidant diets are complicated by the difficulty of interpreting food labels 
and the presence of undeclared or hidden allergens in commercially prepared foods 
(Joshi et al, 2002; Altschul et al, 2001; Vierk et al 2002). Accidental exposures are common, 
with up to 50 percent of food-allergic patients having ≥ 1 allergic reaction over a 2-year 
period (Sicherer et al, 1998). 
In early clinical trials, oral immunotherapy (OIT) for peanut allergy has demonstrated 
encouraging safety and efficacy results in creating a change in clinical reactivity that would 
protect recipients from these accidental exposures (Jones et al, 2009; Hofmann et al, 2009; 
Blumchen et al, 2010; Yu et al, 2012; Varshney et al, 2011; Anagnostou et al, 2014). These 
studies involved a period of up-dosing with increasing amounts of peanut protein, a period of 
maintenance therapy, and then an oral food challenge (OFC) to assess desensitization. 
Dosing symptoms observed in these studies have included rash, wheezing, rhinorrhea, 
sneezing, itching, abdominal pain, nausea, vomiting, and diarrhea. Most symptoms have been 
mild, consistent with a transient, low-grade allergic reaction, and have tended to diminish in 
frequency with increasing duration of treatment.  
There is evidence that OIT induces a clinically meaningful level of desensitization in most 
subjects and may also induce favorable immunologic changes over time. Though these 
studies used different doses and regimens, they collectively provide supportive evidence for 
the efficacy and safety of peanut OIT and were the basis for the initiation of clinical 
development of AR101, a well-characterized oral desensitization immunotherapy 
investigational product that is manufactured under current Good Manufacturing Practice 
(cGMP) and previously tested in Aimmune’s Phase 2 program.  
The goal of OIT with AR101 is to induce and maintain a state of desensitization to peanut 
protein, defined as the ability to consume a specific dose of peanut protein with no or mild 
symptoms. This state of desensitization, in conjunction with a peanut-avoidant diet, should 
be sufficient to protect a peanut-allergic individual from an accidental exposure to peanuts or 
peanut-containing foods.  

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1.2 
Clinical Trials of AR101 
1.2.1 
ARC001 
ARC001 was a phase 2, multicenter, randomized, double-blind, placebo-controlled study of 
the efficacy and safety of AR101 in peanut-allergic children and adults 4 to 26 years of age. 
ARC001 consisted of a screening period (including a screening double-blind, 
placebo-controlled food challenge [DBPCFC]), an initial escalation period, an up-dosing 
period, and a maintenance period, followed by an exit DBPCFC. The primary endpoint of 
ARC001 was the percentage of desensitization responders, defined as subjects tolerating 
300 mg of peanut protein (443 mg cumulative) at the exit DBPCFC. 
A total of 56 subjects were randomized: 29 subjects to AR101 and 27 subjects to placebo. 
One subject withdrew consent after randomization and before treatment. The intent-to-treat 
(ITT) population thus comprised 55 subjects: 29 in the AR101 group and 26 in the placebo 
group. The 2 groups were overall well matched for baseline characteristics, including 
baseline sensitivity in the screening DBPCFC. Six subjects in the AR101 arm withdrew prior 
to the exit DBPCFC.  
In the ITT population, AR101 was significantly superior to placebo, with 23 of 29 (79%) 
desensitization responders as compared to 5 of 26 (19%) desensitization responders in the 
placebo group, resulting in a treatment difference of 60% (p < 0.0001 by Fisher exact test). In 
the completer population (those subjects reaching the exit DBPCFC), 23 of 23 AR101 
completers were desensitization responders, resulting in a treatment difference of 81% 
(p < 0.0001 by Fisher exact test). 
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 study product. An additional subject experienced a non-treatment-emergent 
SAE of anaphylactic reaction following the screening DBPCFC. Four (14%) AR101-treated 
subjects discontinued due to adverse events (AEs), with either hypersensitivity (n = 3) or 
vomiting (n = 1) being the most common AEs leading to discontinuation. Two additional 
AR101 subjects discontinued due to treatment-related reasons that included gastrointestinal 
(GI) AEs, but not exclusively. No placebo subjects discontinued due to an AE. The most 
commonly occurring TEAE in all subjects 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%). 
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 
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.  

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1.2.2 
ARC002 
All placebo subjects who completed ARC001 were eligible for rollover into the open-label 
ARC002 study. Placebo subjects in ARC002 underwent an escalation 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 also eligible to enter ARC002.  
Group 1 included subjects who completed the placebo arm of ARC001 and consented to 
enroll in ARC002, crossing over to active treatment using the same dosing regimen used in 
ARC001, but in open-label fashion. After completion of the buildup phase, Group 1 subjects 
underwent a DBPCFC (to a maximum single dose of 600 mg of peanut protein, or 1043 mg 
of cumulative peanut protein). Subjects who did not tolerate the post-low-dose buildup phase 
DBPCFC at ≥ 443 mg were considered escalation failures and were discontinued from the 
study for safety considerations. Those subjects who tolerated the DBPCFC at ≥ 443 mg of 
peanut protein entered an approximately 3-month (12- to 24-week) plateau phase of 
continued dosing at 300 mg/d. Group 2 subjects completed the active AR101 arm of 
ARC001 and consented to enroll directly into the 300 mg/d, 3-month plateau phase of 
ARC002. Following completion of the 3-month plateau phase, subjects underwent 
a post-plateau phase DBPCFC (to a maximum single dose of 1000 mg of peanut protein, or 
2043 mg cumulative). 
Based on the total population of 26 Group 1 subjects receiving ≥ 1 dose of AR101, 76.9% of 
subjects tolerated 300 mg and 65.4% tolerated 600 mg. At the post-plateau DBPCFC in 
40 subjects in Groups 1 and 2, 100%, 90%, and 60% of the subjects tolerated a cumulative 
peanut protein dose of 443 mg, 1043 mg, and 2043 mg, respectively. These findings 
demonstrate the persistence of desensitization during daily maintenance treatment with 
AR101 at 300 mg/d, further supporting the primary endpoint selection in the ongoing phase 3 
trial ARC003. They also indicate that treatment with AR101 may achieve a maximum 
tolerated dose of food allergen substantially higher than the dose used for maintenance itself. 
The overall profile of AEs observed in ARC002 is highly consistent with what was observed 
in ARC001 and with what has been reported in the literature for academic peanut OIT 
clinical trials. These findings continue to support the ongoing clinical development of 
AR101, and in particular, the safety of low-dose maintenance treatment at 300 mg/d. 
1.2.3 
ARC003 
ARC003 is an international, multicenter, randomized, double-blind, placebo-controlled study 
of the efficacy and safety of AR101 in a characterized desensitization OIT regimen in 
peanut-allergic individuals. The study consists of a screening phase that includes a screening 
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 will 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 (~24 weeks). Subjects who do not reach 

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300 mg/d will be considered escalation failures and nonresponders for the primary analysis. 
Each subject will be unblinded when he/she completes the DBPCFC at the end of the 
approximately 24-week maintenance period and all major data queries for the subject have 
been resolved. Those who do not pass the DBPCFC at ≥ 443 mg cumulative challenge dose 
level will be considered endpoint failures and nonresponders for the primary analysis.  
1.3 
Rationale for the Current Study 
ARC004 is designed as a follow-on study of ARC003. The study population will therefore be 
based on the ARC003 study population: approximately 500 international peanut-allergic 
children and adults (ages 4 to 55 years, inclusive). Three main considerations inform the 
design of the current study ARC004. The first is to allow placebo-treated subjects from 
ARC003 to have the opportunity to access active treatment with AR101. The second is to 
prolong treatment periods with AR101 in order to continue assessment of its safety and 
efficacy profile. Finally, ARC004 is specifically designed to begin exploring alternate 
(eg, nondaily) OIT extended maintenance dosing regimens. Because no previous peanut OIT 
studies have formally examined nondaily dosing intervals, no published preliminary data 
exist to provide guidance. Therefore, the data generated in ARC004 are expected to be 
exploratory and hypothesis-generating, and to have the potential to shape a larger subsequent 
study to confirm the observations made in ARC004 of nondaily dosing regimens. 
The rationale for extending the interval between OIT doses is primarily derived from the 
roughly 100 years of accumulated clinical expertise with subcutaneous immunotherapy 
(SCIT), as encoded in the current SCIT practice parameter documents (Cox et al, 2011). 
Patients taking SCIT for environmental and/or Hymenoptera venom allergies are 
conventionally started on schedules that begin, in the up-dosing phase, with doses 
administered once or twice per week, or in some cases even more frequently (eg, “rush” or 
“cluster” immunotherapy). As patients become hyposensitized and achieve their target 
maintenance dose, the intervals between injections are then lengthened to monthly during the 
maintenance period, with no loss of clinical efficacy or increase in AEs. In turn, this 
conventional monthly maintenance schedule lessens the substantial logistical and economic 
burdens on patients and families and helps to ensure long-term adherence. While adherence 
to therapy is important in all disease contexts, it is especially critical in immunotherapy, 
a modality that requires periodic antigen administration over the span of years to reprogram 
immune responses and clinically improve chronic conditions. 
By contrast, there is little to no evidence from food immunotherapy studies to determine 
what effects, if any, the alteration of OIT dosing schedules would have on peanut-allergic 
individuals and families. ARC004 is one of the first studies to address this question. In 
contrast to the SCIT experience, when intervals between doses can be safely lengthened once 
participants achieve the completion of the up-dosing period, all peanut OIT studies published 
to date have continued daily dosing. Given the absence of data to suggest otherwise, it has 
been an accepted convention that subjects must take their doses every day unless doing so 
would create undue risk (eg, in the presence of an intercurrent viral infection, which has been 
shown to lower thresholds for allergic reactions). This historical convention also informed 
the AR101 Phase 2 program, in which all doses were intended to be administered daily. 

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Nonetheless, the Phase 2 protocols allowed for dose to be withheld for up to 3 days, or more 
as necessary, at the discretion of the investigator due to the presence of intercurrent illness. 
This provides some preliminary clinical evidence that dosing need not necessarily occur daily 
to maintain the level of desensitization.  
Furthermore, published work from Dr. A. Wesley Burks’ research group suggests that 
2 to 5 years of peanut OIT can lead to mechanistic changes and “sustained 
unresponsiveness,” allowing safe consumption of 5 grams of peanut protein after a 1-month 
hiatus from dosing (Vickery et al, 2014; Vickery et al, 2016). Yet preliminary unpublished 
evidence suggests that even after as little as 6 months of OIT treatment (ie, only the 
up-dosing phase and a brief maintenance period), subjects may tolerate peanut exposures 
spaced 1 or more weeks apart (personal communication, A.W. Burks). If true, this would 
suggest that, once desensitized, exposures to therapeutically administered peanut allergens 
need not occur every day, as has already been shown for milk (Pajno et al, 2013) and, as 
described above, Hymenoptera.  
The exit DBPCFC of ARC004 will include a final dose of 2000 mg of peanut protein (up to 
a cumulative dose of 4043 mg).  Phase 2 results and peer-reviewed studies published in the 
medical literature indicate that subjects tolerating a maintenance dose of 300 mg of peanut 
protein for 6 months are able to tolerate higher amounts of peanut protein during the exit 
challenge (Jones et al, 2009; Vickery et al, 2017). 
It has been previously observed that AR101 was well tolerated and appeared to reproducibly 
induce desensitization to peanut when used daily. The goal of ARC004 is to examine 
whether intermittent dosing of AR101 during extended maintenance can preserve the 
desensitization gained by daily dosing; and if so, how much daily treatment is advisable 
before the interval can be adjusted. In the short term, the data gained from this study should 
provide very practical guidance to assist physicians in determining how to manage short-term 
dosing interruptions. Longer term, the results will have key implications for designing 
maintenance therapy regimens in future AR101 development protocols.  
1.4 
Known and Potential Risks and Benefits of AR101 
1.4.1 
Risks 
Peanut is a commonly consumed food and as such has a well-understood safety profile. 
Except for allergic reactions in subjects with peanut allergy, it does not cause discernible side 
effects in humans. 
In subjects with peanut allergy, there have been many OIT studies 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 the 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 

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esophagitis (EoE), affecting an estimated 3 to 4% of OIT recipients (Lucendo et al, 2014), 
which is thought to be reversible upon stopping dosing. 
The buildup 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 buildup of dosing under observation in a clinical 
setting until the maintenance dose is achieved. 
Oral food challenges may induce an allergic response. Allergic reactions can be severe, 
including life-threatening allergic reactions; however, the risk of an allergic reaction is 
reduced by initiating the challenge with a very small amount of the food, gradually 
increasing the dose, and stopping the challenge at the first sign of a reaction. If subjects have 
allergic reactions during the challenges, they may need oral, intramuscular (IM), 
or intravenous (IV) medications, and will be treated per study center standard of care. 
Trained personnel, including a physician, as well as medications and equipment (per 
PRACTALL recommendations and investigational site standard operating procedures), will 
be immediately available to treat any reaction. The anticipated rate of serious life-threatening 
anaphylactic reactions was < 0.1%, and none were seen during food challenges in the Phase 2 
program.  
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 
family will be warned that they should continue to practice their usual vigilance against 
accidental ingestion of peanuts or peanut-containing foods. 
1.4.2 
Benefits 
There is no guarantee that participation in this study will help a subject. Information from 
this study may help researchers to better understand peanut allergy or to develop future tests 
or treatments to help patients with this condition. 
Please refer to the current edition of the AR101 Investigator’s Brochure for further 
information regarding the safety profile, risks, and benefits of AR101.  
2 OBJECTIVES 
2.1 
Primary Objective 
The primary objective of this study is to determine the safety, tolerability, and efficacy of 
AR101 characterized oral desensitization immunotherapy (CODITTM) using alternative 
maintenance dosing intervals. 

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2.2 
Secondary Objectives 
The secondary objectives are: 
• 
To confirm the safety profile of AR101 as measured by the incidence of AEs, 
including SAEs 
• 
To confirm the efficacy of AR101 through reduction in clinical reactivity, measured 
in a DBPCFC to a cumulative dose of 4043 mg  
• 
To evaluate subjects’ QoL and treatment satisfaction during AR101 treatment on 
daily and nondaily treatment regimens  
• 
To evaluate the long-term immunologic effects of AR101 treatment 
3 STUDY DESIGN 
This is an international, multicenter, open-label, 2-arm follow-on study of ARC003. The 
2 arms to be studied in ARC004 are the subjects who received placebo in ARC003 (Group 1) 
and those who received AR101 in ARC003 (Group 2).  
Group 1 (Placebo Crossovers): Subjects who complete the placebo arm of ARC003 are 
eligible to enroll in ARC004. All placebo subjects who consent to participate in ARC004 will 
enter Group 1 and will undergo initial escalation, up-dosing, and maintenance with AR101, 
as in the active arm of ARC003. The Initial Escalation Period consists of a step-wise 
dose-escalation from 0.5 to 3 or 6 mg (as tolerated) on Day 1 and confirmation of the ability 
to tolerate a single dose of 3 mg on Day 2. The Up-dosing Period is 22 to 40 weeks in 
duration and consists of dose escalations every 2 weeks up to a maximum of 300 mg/d (as 
tolerated). The Maintenance Period consists of daily dosing at 300 mg/d for approximately 
24 weeks, at which point Group 1 subjects will undergo a DBPCFC to a maximum total of 
4043 mg cumulative peanut protein to test the efficacy of AR101 in desensitizing ARC003 
placebo crossovers to large amounts of peanut protein after 6 months of daily maintenance.  
All Group 1 subjects tolerating ≥ 443 mg of cumulative peanut protein in this challenge will 
be eligible to continue in ARC004, and enter the Extended Maintenance (EM) Period, 
initially consisting of ongoing daily maintenance therapy at 300 mg/d. Dependent upon the 
EM results from ARC004 Group 2 (below), subjects in Group 1 EM will test the gradual 
lengthening of their dosing interval from once daily (QD) to every other day (QOD), twice 
weekly (BIW), once weekly (QW), and finally every other week (QOW), as tolerated. The 
length of each interval will be between 8 and 24 weeks and will be adjusted based on the data 
from Group 2. Lengthening to each level will occur sequentially (QD then QOD then BIW 
then QW and finally QOW), and only if sufficient evidence exists, based on the analyses of 
the Group 2 EM subjects and the ongoing safety of Group 1 subjects, to support progression 
to each level.  
Group 2 (Active Rollovers): Subjects who complete the active arm of ARC003 and tolerate a 
challenge dose of ≥ 443 mg cumulative of peanut protein at the ARC003 Exit DBPCFC are 
eligible to enroll in ARC004. Group 2 subjects will have undergone the Initial Escalation, 

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Up-dosing, and Maintenance Periods in ARC003 and will therefore enter the ARC004 EM 
period directly. 
Upon entry into the EM phase of the study, Group 2 subjects will be consecutively enrolled 
into 1 of several cohorts that will conditionally explore an alternate dosing interval regimen 
over 28-week study periods, as follows:  
 EM Cohort 1: The first 120 Group 2 subjects to enter ARC004 will comprise Cohort 1, 
and will continue 300 mg of AR101 QD for 28 weeks before undergoing an Exit 
DBPCFC (total 28 weeks).  
 EM Cohort 2: The next 50 Group 2 subjects (subjects 121-170) enrolling in ARC004 
will comprise Cohort 2 and will take 300 mg of AR101 QOD for 4 weeks and then BIW 
(eg, Monday/Thursday) for 24 weeks (total of 28 weeks) as tolerated, before undergoing 
an Exit DBPCFC.  
 EM Cohort 3: All remaining subjects recruited into ARC004 (subjects 171 to the end) 
will comprise Cohort 3. This cohort will be randomized 1:1:1 to 1 of 3 initial strategies:  
a. 300 mg QD for 56 weeks followed by an Exit DBPCFC (Cohort 3A) (total 56 weeks) 
b. 300 mg QD for 28 weeks, then 300 mg QOD for 4 weeks, then BIW for 24 weeks, as 
tolerated, followed by an Exit DBPCFC (Cohort 3B) (total 56 weeks) 
c. 300 mg QD for 28 weeks, then 300 mg QOD for 4 weeks, then BIW for 24 weeks, 
then 300 mg QW for 28 weeks, as tolerated, followed by an Exit DBPCFC 
(Cohort 3C) (total 84 weeks) 
In ARC004, Exit DBPCFCs will test to a maximum of 4043 mg cumulative peanut protein to 
determine the continued efficacy of each alternate dosing schedule. Following the 
end-of-study visit, each subject’s participation in ARC004 ends. The end of the study is 
defined as the date of the last visit of the last subject. 
End of Participation in ARC004 and Entry into ARC008:  After the end of participation in 
ARC004, subjects may enroll in the long-term, open-label extension study ARC008 to 
continue treatment with AR101 at their current dosing regimen (QD, BIW, QW, or QOW) or 
switch to AR101 daily dosing, until AR101 becomes commercially available or ARC008 is 
terminated, as follows:  
• 
Subjects on any dosing regimen able to tolerate at least the 600 mg single dose of 
peanut protein (≥ 1043 mg cumulative) at their ARC004 Exit DBPCFC will continue 
their current dosing regimen in Treatment Pathway 1 of ARC008 when that study is 
available. If ARC008 is not available at the study site, these subjects may continue 
their current dosing regimen and have visits in ARC004 until they can enroll in 
ARC008.  
• 
Subjects who tolerate their alternate (eg, nondaily) dosing regimen and tolerate at 
least the 300 mg single dose of peanut protein (≥ 443 mg cumulative) but are unable 
to tolerate the 600 mg single dose of peanut protein (1043 mg cumulative) at the 
ARC004 Exit DBPCFC will switch to daily dosing with 300 mg AR101 in Treatment 
Pathway 1 of ARC008, per investigator discretion. If ARC008 is not available at the 

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study site, these subjects may start AR101 daily dosing and have visits in ARC004 
until ARC008 is available, then continue dosing in ARC008.  
• 
Subjects on a nondaily dosing regimen who tolerate less than the 300 mg single dose 
of peanut protein (443 mg cumulative) at the Exit DBPCFC may be eligible for 
treatment in ARC008 per investigator judgment and after discussion with the medical 
monitor. If continued treatment with AR101 is determined to be safe, these subjects 
will have the option to receive AR101 daily in Treatment Pathway 2 of ARC008, 
which consists of Repeat Up-dosing (dose escalation from 80, 120, or 160 mg to 
300 mg daily), Initial Maintenance, and Extended Maintenance. If ARC008 is not yet 
available or able to accept these subjects at the study site, these subjects may start 
AR101 daily dosing and have visits in ARC004 until they can enroll in ARC008.  
• 
Subjects who do not tolerate their nondaily dosing regimen (Section 7.8.2) will have 
the option to receive AR101 daily in Treatment Pathway 2 of ARC008, which 
consists of Repeat Up-dosing (dose escalation from 80, 120, or 160 mg to 300 mg 
daily), Initial Maintenance, and Extended Maintenance. If ARC008 is not available at 
the study site, these subjects may start AR101 daily dosing and have visits in 
ARC004 until ARC008 is available, then continue dosing in ARC008.  
• 
Subjects on a nondaily dosing regimen who miss or withhold their dose for > 3 days, 
including subjects receiving QOD, BIW, or QW dosing who miss or withhold their 
dose for > 14 days, will have the option to receive AR101 daily in Treatment 
Pathway 2 of ARC008, which consists of Repeat Up-dosing (dose escalation from 80, 
120, or 160 mg to 300 mg daily), Initial Maintenance, and Extended Maintenance. If 
ARC008 is not available at the study site, these subjects may start AR101 daily 
dosing and have visits in ARC004 until they can enroll in ARC008.  
Subjects are not eligible to enroll in ARC008 when continued treatment with AR101 is 
determined to be unsafe as follows: 
• 
Subjects on a daily dosing regimen who are unable to tolerate at least the 300 mg 
single dose of peanut protein (443 mg cumulative) at the Exit DBPCFC.  
• 
Subjects not tolerating their nondaily dosing regimen (Section 7.8.2) who begin 
Repeat Up-dosing in ARC004, but are unable to dose escalate to AR101 300 mg daily 
and tolerate that dose level for 2 weeks within 26 weeks.  
3.1 
Study Periods 
The ARC004 study consists of 4 study periods: 
• 
Initial Escalation - Group 1 only 
• 
Up-dosing - Group 1 or Repeat Up-dosing for subjects switching to a daily AR101 
dosing regimen (Section 3) at a study site that has not yet received approval to enroll 
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• 
Maintenance - Group 1 and subjects switching to a daily AR101 dosing regimen and 
who completed Repeat Up-dosing at a study site that has not yet received approval to 
enroll these subjects in ARC008 
• 
Extended Maintenance - Groups 1 and 2 
3.1.1 
Initial Escalation (Group 1 Only) 
All Initial Escalation doses will be administered by investigational site personnel under direct 
observation. Eligible subjects will initiate treatment with AR101 on Day 1, starting at a dose 
of 0.5 mg, increasing the dose at 20 to 30 minute intervals to a maximum dose of 6 mg 
(Table 1). Subjects who fail to tolerate ≥ 3 mg dose on Day 1 will be considered escalation 
failures and will be discontinued. Subjects who tolerate ≥ 3 mg dose on Day 1 will undergo 
confirmatory dosing of a single 3 mg dose on Day 2. Subjects who do not tolerate this 
confirmatory dose will be discontinued. Subjects who tolerate this confirmatory dose will 
enter the Up-dosing Period.  
Table 1: Initial Escalation Schedule (Group 1 Subjects Only) 
Initial Escalation Schedule (Group 1 only) 
Day 1 
Dose Number 
AR101 Dose, mg* 
Cumulative AR101 Dose, mg 
1 
0.5 
0.5 
2 
1 
1.5 
3 
1.5 
3 
4 
3 
6 
5 
6 
12 
Day 2 
Dose Number 
AR101 Dose, mg 
Cumulative AR101 Dose, mg 
1 
3 
3 
*All mg doses shown refer to milligrams of peanut protein. 
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. 
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. 
 
3.1.2 
Up-dosing (Group 1 Only) 
Subjects will receive AR101 starting at a dose of 3 mg once daily and gradually escalating 
every 2 weeks to a maximum of 300 mg once daily, according to the Up-dosing Maintenance 

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Schedule (Table 2). All escalation doses will be administered under direct observation; 
subsequent doses will be dispensed to the subject/guardian and administered at home. Doses 
may be adjusted for tolerability or intercurrent illness; the Up-dosing period may thereby be 
extended to a maximum of 40 weeks. Subjects unable to escalate to 300 mg within 40 weeks 
will be considered escalation failures for analysis purposes. Subjects able to escalate to 
300 mg and maintain this dose regimen for 2 weeks will have completed Up-Dosing and will 
enter the Maintenance Period. 
Table 2: Up-dosing Maintenance Schedule (Group 1 Subjects Only) 
Up-dosing and Maintenance Schedule (Group 1 only) 
Dose Number 
AR101 Dose, mg 
Interval (weeks) 
Percent Increase from previous 
dose 
1 
3 
2a 
n/a 
2 
6 
2 
100 
3 
12 
2 
100 
4 
20 
2 
67 
5 
40 
2 
100 
6 
80 
2 
100 
7 
120 
2 
50 
8 
160 
2 
33 
9 
200 
2 
25 
10 
240 
2 
20 
11 
300 
2 
25 
a 
Interval includes Day 2 of Initial Escalation. 
n/a = not applicable. 
 
3.1.3 
Repeat Up-dosing (Subjects Switching to Daily Dosing) 
If a subject meets the criteria for switching to AR101 daily dosing and is at a study site that 
has not yet received approval to enroll these subjects in ARC008, the subject may begin daily 
dosing and have visits in Repeat Up-dosing in ARC004 until they can enroll in ARC008 
(Section 3). If ARC008 is available, the subjects will complete an Exit/Early Discontinuation 
visit in ARC004 and enroll in ARC008.  
Subjects entering the Repeat Up-dosing Period will start with a daily dose of either 80, 120, 
or 160 mg at the discretion of the investigator.  The dose will be increased every 2 weeks as 
per Table 3, until the subject reaches the target dose of 300 mg daily. 
To escalate to the next dose, subjects must be tolerating the current dose. Some subjects may 
require de-escalation, and once the lower dose is tolerated they may again attempt to proceed 
with up-dosing.  To allow for a personalized titration of dosing, the Repeat Up-dosing Period 
will last for a maximum of 26 weeks. Subjects who are not able to achieve the target dose of 

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300 mg/day and tolerate that dose level within 26 weeks will be discontinued from AR101 
dosing and complete an Early Discontinuation Visit; these subjects will not be eligible to 
participate in ARC008.   
Subjects who reach the target maintenance dose of 300 mg and maintain this dose for at least 
2 weeks (maximum duration of Repeat Up-dosing of 26 weeks) will exit ARC004 and enter 
ARC008 when it is available. If ARC008 is not available at the time the subject expects to 
exit ARC004, subjects will continue daily dosing and have visits in ARC004 until ARC008 
is available, then continue dosing in ARC008.  
Table 3: Repeat Up-dosing Schedule (Subjects Switching to Daily Dosing) 
Repeat Up-dosing Schedule (Subjects Switching to Daily Dosing) 
Investigational Product Dose, mga 
Interval (weeks) 
80 
2 
120 
2 
160 
2 
200 
2 
240 
2 
300 
2 
a 
All mg doses shown refer to milligrams of peanut protein. 
 
3.1.4 
Maintenance 
Subjects entering the Maintenance Period will continue AR101 300 mg once daily, 
undergoing directly observed dosing at 12 and 24 weeks. Down-dosing may be necessary 
during the Maintenance Period due to safety or tolerability reasons, but such subjects will 
remain in the Maintenance Period even if they are temporarily taking a dose of less than 
300 mg. The duration of the Maintenance Period does not reset if this occurs.  After 
approximately 24 weeks of daily AR101 treatment at 300 mg in the Maintenance Period, 
Group 1 subjects will undergo a Post-Maintenance DBPCFC with a maximum dose of 
2000 mg of peanut protein (4043 mg cumulative), according to the DPBCFC Schedule 
(Table 4).  Subjects who do not tolerate ≥ 300 mg peanut protein (443 mg cumulative) will 
be considered treatment failures and will be discontinued. Subjects who tolerate ≥ 300 mg 
peanut protein (443 mg cumulative) will enter the EM and continue taking 300 mg/d of 
AR101 until the results of the alternate regimens explored in Group 2 subjects are known.  

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Table 4: DBPCFC Schedule (All Time Points) 
DBPCFC Schedule (All Time Points) 
Challenge Dose, mg 
Cumulative Dose, mg 
3 
3 
10 
13 
30 
43 
100 
143 
300 
443 
600 
1043 
1000 
2043 
2000 
4043 
 
3.1.5 
Extended Maintenance 
The EM periods will differ between and within the 2 groups in duration and dosing regimen 
(see below and Figure 1). However, all EM subjects who complete their dosing regimen, 
regardless of group or cohort assignment, will have an Exit DBPCFC up to a single highest 
dose of 2000 mg of peanut protein (4043 mg cumulative).  
Group 1 
All Group 1 subjects who tolerate ≥ 443 mg cumulative peanut protein in the 
Post-Maintenance DBPCFC will enter the EM period. Subjects who do not tolerate ≥ 443 mg 
are not eligible to continue for safety reasons. The EM period for Group 1 subjects will 
initially consist of QD dosing while the Group 2 cohorts are undergoing evaluation as 
outlined below. Conditional upon the safety and DBPCFC outcomes assessed in the Group 2 
participants, Group 1 subjects may have their dosing interval serially lengthened from QD to 
QOD, QOD to BIW, BIW to QW, and QW to QOW, as tolerated. The duration of each of 
these interval extension periods will be adjusted, based on Group 2’s experience, from 
between 8 to 28 weeks, as tolerated. In clinic visits during the EM for Group 1 subjects will 
continue to occur every 14 weeks. Following the completion of the longest tested dosing 
interval, Group 1 subjects will then undergo an Exit DBPCFC and ARC004 will conclude. 
Group 2 
As they enter ARC004, Group 2 subjects will be consecutively assigned to 1 of 3 cohorts and 
continue to receive AR101 in the following fashion: 
• 
The first 120 Group 2 subjects (ie, 1 to 120) entering ARC004 will form Cohort 1 and 
continue to receive QD treatment for 28 weeks as tolerated and then undergo an Exit 
DBPCFC. 

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• 
The next 50 Group 2 subjects (ie, 121 to 170) entering ARC004 will form Cohort 2, 
receiving AR101 300 mg QOD for 4 weeks, and then BIW for 24 weeks, as tolerated, 
and then undergoing an Exit DBPCFC. 
• 
All remaining Group 2 subjects (ie, 171 to end) entering ARC004 will form Cohort 3. 
Upon entering Cohort 3, these subjects will be randomized 1:1:1 to receive AR101 in 
28 week periods, as follows. Cohort 3A will receive 300 mg QD for 56 weeks as 
tolerated and then undergo an Exit DBPCFC. Cohort 3B will receive 300 mg QD for 
28 weeks and then 300 mg QOD for 4 weeks followed by BIW for 24 weeks, as 
tolerated, and then undergo an Exit DBPCFC. Cohort 3C will receive 300 mg QD for 
28 weeks, 300 mg QOD for 4 weeks followed by BIW for 24 weeks, and then 300 mg 
QW for 28 weeks, as tolerated, and then undergo an Exit DBPCFC. 
Throughout ARC004 EM, the first 2 doses at extended nondaily dosing intervals (BIW, QW, 
QOW) will always be administered under direct supervision in the clinic; QOD dosing is an 
exception and can be initiated at home. Thereafter, the doses will be administered at home as 
tolerated, and recorded in the subject diary. Investigators may, at their discretion, bring 
subjects back to the research unit for an observed dose at any time. All AR101 doses will be 
judged by the investigator to be tolerated or not tolerated according to criteria previously 
established in ARC003 and specified in Section 6.5.2. 
Dosing intervals should be as consistent as possible, preferably on the same days each week.  
• 
In the BIW group, doses should be at least 3 days apart (eg. Monday and Thursday 
each week) 
• 
In the QW group, doses should be taken on the same day (± 1 day) each week 
• 
In the QOW group, doses should again be taken on the same day (± 2 days), every 
other week  
Any subject receiving nondaily dosing (QOD, BIW, QW, or QOW) who has 1 related SAE; 
1 related AE graded severe; 2 related AEs occurring on separate occasions, both graded 
moderate; or 3 consecutive doses judged “not tolerated,” will be considered a treatment 
failure in the statistical analysis of each cohort. These subjects will be returned to a 300-mg 
daily regimen by entering the Repeat Up-dosing period. For the majority of subjects, Repeat 
Up-dosing will be carried out in Treatment Pathway 2 of ARC008. However, if ARC008 is 
not available at the study site, subjects may start AR101 daily dosing and have visits in 
ARC004 until ARC008 is available, then continue dosing in ARC008.  
No subject will be exposed to a longer dosing interval if evidence from previous cohorts 
suggests that doing so would more likely than not cause the subject to either experience more 
frequent or more severe AEs, or lose desensitization that he or she may have 
gained/maintained, compared to more frequent dosing. Because subjects in Cohorts 3B and 
3C will have had 28 additional weeks of QD maintenance treatment, these subjects will be 
allowed to proceed to QOD and BIW dosing independent of Cohort 2’s experience according 
to the judgment of the Safety Monitoring Committee (SMC).  

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Aimmune will monitor the safety and efficacy in each of the cohorts in accordance with 
internal procedures and escalate to the internal Safety Monitoring Committee (SMC) for 
review and recommendation for action. Only when sufficient efficacy and safety evidence is 
available on a cohort, will the SMC recommend that the next cohort advance to a longer 
interval between doses. Therefore, only after the safety and efficacy data from Group 2 
cohorts are available, reviewed, and approved by the SMC, will the SMC allow the Group 1 
patients to modify their once-daily regimen.  
For more information on individual-, cohort-, and study-stopping rules, see Section 7.8. 
Down-dosing may be necessary during the Extended Maintenance Period due to safety or 
tolerability reasons; however subjects who had to be down-dosed remain in the Extended 
Maintenance Period during the dose adjustment. The duration of the Extended Maintenance 
Period does not reset if this occurs.   
Early Discontinuations 
Subjects who are discontinued and who do not enter ARC008 will be followed for safety for 
a minimum of 30 days after the last dose of AR101, 2 weeks after the last food challenge, or 
until resolution or stabilization of all AEs ongoing at the time dosing is stopped, whichever is 
longer. In addition, subjects who are discontinued from further AR101 dosing due to chronic 
or recurrent GI AEs will have experienced an AE of interest (AEI) and will be followed 
monthly for a minimum of 6 months, or until resolution or stabilization of all GI AEs 
(Section 7.3.3.2 for more information about GI AEIs).  
For subjects who do not tolerate their nondaily dosing regimen and subjects who switch to 
daily dosing after missing their nondaily dose for > 3 days, the exit DBPCFC will be omitted 
before discontinuation from ARC004 and enrollment in ARC008.  
Subjects who are discontinued will not be replaced. 
4 SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Inclusion Criteria 
Subjects who meet all of the following criteria are eligible: 
 Completion of ARC003 
 Written informed consent and/or assent from subject/guardian as appropriate  
 Use of effective birth control by female subjects of child-bearing potential 
(Section 7.7.3.2) 
4.2 
Exclusion Criteria 
Subjects who meet any of the following criteria are not eligible: 
 Early discontinuation from ARC003 

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 Meets any longitudinally applicable ARC003 exclusion criteria (Appendix 7) 
 (Group 2 only) Failure to tolerate 443 mg cumulative of peanut protein with no or mild 
symptoms in the ARC003 Exit DBPCFC 
 Any other condition that, in the opinion of the investigator, precludes participation for 
reasons of safety 
4.3 
Early Termination 
4.3.1 
Criteria for Early Termination 
Any subject will be prematurely terminated from additional study drug treatment and 
excluded from any further study procedures (except for safety follow-up) for any one the 
following reasons: 
 Life-threatening symptoms (Consortium of Food Allergy Research [CoFAR] Grade 4; 
refer to 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 
 Severe allergic hypersensitivity symptoms (CoFAR Grade 3; refer to Appendix 4), 
including, but not limited to, those that require intensive therapy (to be determined by the 
investigator, but may include such interventions as intravenous (IV) epinephrine, 
intubation, or admission to an intensive care unit) or those that are recurrent. 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. 
 Pregnancy  
 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 safety 
issue (QD regimens only) 
 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 (Group 1 only) 
 The subject elects to withdraw consent from all future study activities, including 
follow-up. 
 The subject is “lost to follow-up” (ie, no further follow-up is possible because attempts to 
reestablish contact with the subject have failed). 
 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. 
 The subject dies (CoFAR Grade 5). 

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 Poor control or persistent activation of secondary atopic disease (eg, atopic dermatitis, 
asthma)  
 Started on angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) 
inhibitors, beta-blockers, or other prohibited medications, with no alternative medications 
available per the prescribing doctor 
 The subject develops biopsy-documented eosinophilic esophagitis (EoE) 
Subjects who discontinue study product 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 
Subjects who prematurely discontinue treatment will be brought in for an Early 
Discontinuation Visit approximately 14 days after their last dose of study product. 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 discontinue treatment due wholly or in part to GI AEs will be instructed to 
complete the Pediatric Eosinophilic Esophagitis Symptom Scores (PEESSTM v2.0) 
questionnaire (Franciosi et al, 2011) monthly for 6 months. These subjects will also be asked 
to continue to fill out their daily diary for the same 6-month duration. Additional instructions 
for the follow-up of subjects who discontinue treatment due wholly or in part to GI AEs is 
contained in Section 7.3.3.2.  
4.3.3 
Subject Replacement 
No subject who is randomized or enrolled in this trial and who undergoes early termination 
will be replaced. 
5 STUDY TREATMENT 
5.1 
Formulation, Packaging, and Labeling 
The active study product AR101 (characterized peanut allergen) is in the form of peanut flour 
formulated with a bulking agent and a flow agent in pre-measured graduated doses 
comprising break-apart capsules containing 0.5, 1.0, 10, 20, and 100 mg each of peanut 
protein. Capsules containing study product will be provided in pre-packaged bottles or blister 
cards assembled into dosing kits for Up-dosing. Each individual bottle or blister of a blister 
card will contain a single day’s dose of study product. For daily dosing regimens, each kit 

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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. Kits for nondaily regimens 
may be modified accordingly and will also contain overages allowing for visit flexibility. For 
the Maintenance and EM periods, AR101 will be provided in foil-lined sachets at a dose of 
300 mg.  
Study product is characterized with a high-performance liquid chromatography (HPLC) 
fingerprint and specific enzyme-linked immunosorbent assays (ELISAs) performed against 
key allergenic proteins to demonstrate stability and lot-to-lot comparability. 
All study products will be packaged and labeled at the central manufacturer. The study 
products (in blister packets for initial dose escalation and up-dosing and in sachets for 
maintenance dosing) will then be shipped to a drug depot where they will be labeled and 
inventoried for shipment to the clinical sites. Study products will be shipped by the drug 
depot to the investigational site or the investigational site pharmacy, according to 
site-specific institutional policies. Study products will then be distributed to 
subjects/subjects’ parents or guardians by study site personnel. All study products will be 
stored in a secure location and kept refrigerated between 2°C and 8°C.  
5.2 
Preparation, Administration, and Dosage 
The first dose at each new dose level during the Up-dosing Period, and the first 2 doses at 
each extended dosing interval regimen (BIW, QW, and QOW) are to be administered in the 
clinical research center (CRC) under the direct supervision of an appropriately credentialed 
healthcare provider and the oversight of a physician. Once the dose(s) are removed from a 
dosing kit for in-clinic administration, the kit must be dispensed to the subject or held at the 
site for documented destruction or returned to the Sponsor’s designee (as instructed); dosing 
kits once opened cannot be used for any other dosing interval or any other subject. At clinic 
visits, subjects will receive a kit of capsules/sachets to be taken at home according to their 
specific dose level. The subjects will be instructed to document capsules/sachets taken at 
home using subject diary logs and to bring all unused capsules/sachets back to the clinic at 
the next visit. The subjects will be instructed to store the dosing kit in the refrigerator except 
when it is removed to obtain the daily dose.  
Procedures for preparation and administration of doses given in clinic or at home are the 
same. Dose preparation is to be completed by the 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 
delivery of contents. The contents of the capsules/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. Study 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 

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be consumed in a few spoonfuls. The study product should be consumed as promptly after 
mixing as practicable. If not consumed within 4 hours of mixing in a vehicle, the study 
product-vehicle food mixture should be discarded and a new dose mixed prior to 
consumption. 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 study product was 
prepared. If there is a delay of more than 24 hours in consumption, the study product is to be 
discarded and a new study product dose mixed and consumed. It is recommended that each 
dose of study product be taken at a consistent time (within a 4-hour time period) each day 
that the dose is to be taken. A target interval of ≥ 8 hours should pass between doses. Per 
investigator judgment, a home dose may be split into 2 portions for tolerability reasons, 
further discussed in Section 6.5.5.2.  
Except for in-clinic dosing, the daily home dose should be taken as part of a meal. Dosing at 
the evening meal is recommended to permit children to be observed and supervised in the 
home setting by their parents 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, it is crucial that subjects take 
their dose according to their assigned schedule. No attempt should be made to make up for a 
missed QD dose if greater than 6 hours have elapsed since usual time of dosing.  
For subjects on nondaily EM regimens, doses should be administered at approximately the 
same time on the scheduled days. If more than 6 hours has elapsed since the dose was due, 
the dose should be considered missed due to non-adherence, and administered the following 
day (at approximately the same time of day as previously administered). Thereafter, the 
subject should return to the original schedule. Please refer to the Study Manual on return to 
dosing. All administered doses will be entered into dosing logs and reviewed by the site. 
Missed or withheld doses on nondaily EM schedules due to intercurrent AEs represent a 
special situation and are discussed further in Section 6.5.7.  
5.3 
Drug 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 investigational agent, 
including the date and quantity of the drug received, to whom the drug was dispensed 
(subject-by-subject accounting), and a detailed accounting of any drug accidentally or 
deliberately destroyed. 
Records for receipt, storage, use, and disposition will be maintained by the study site. 
A drug-dispensing log will be kept current for each subject. This log will contain the 
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All records regarding the disposition of the investigational product will be available for 
inspection by the clinical trial monitor. 
5.4 
Assessment of Compliance with Study Treatment and Monitoring 
Families will document daily dosing and any reaction to at-home dosing by diary logs. 
Central monitoring of compliance will be performed by comparing returned unused study 
product against the daily dosing records. Families will be provided with 24-hour emergency 
contact information for the site. 
Doses of study product lost or destroyed at home will also be recorded in the diary logs. All 
unused study product should be brought back to the clinic with each visit for reconciliation of 
remaining capsules/sachets.  
5.5 
Modification of Study Treatment 
Study product doses may be adjusted by the study physician if the subject is unable to 
tolerate their scheduled dose level. If such a dose modification occurs requiring dosing at a 
lower dose level, the subject will return all unused capsules/sachets of study product during a 
dose adjustment visit, and be dispensed new capsules at the adjusted dose level. 
5.6 
Concomitant Medications 
Except as indicated in Section 5.10, all subjects may continue their usual medications, 
including those taken for asthma, allergic rhinitis, and atopic dermatitis, during the study. 
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, skin prick testing (SPT), and OFCs. Usual topical steroid use is permitted 
following SPT.  
5.7 
Prophylactic Medications 
Although symptomatic treatments for chronic/recurrent AEs are permitted, as for example 
with H-1 or H-2 histamine blockers, proton pump inhibitors, or beta-adrenergic agonists, 
such medications should, in general, not be started in advance of symptoms; however, 
exceptions can be granted on a case-by-case basis following a mandatory discussion between 
the investigator and the Medical Monitor. If started, the use of these medications should be 
minimized, and then discontinued, at the earliest medically appropriate opportunity.  
5.8 
Rescue Medications 
Treatment of individual acute allergic reactions during ARC004 should be with either 
an antihistamine and/or epinephrine, along with IV fluids, beta-adrenergic agonist 
(eg, albuterol), oxygen, and/or steroids, as indicated. Subjects and parents/guardians are 
likely already to have an epinephrine auto-injector device, but for those who do not, an 
epinephrine auto-injector device will be provided. The expiry dates for the epinephrine 

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auto-injectors should be tracked by the site and subjects/families resupplied as necessary. 
Study staff must document in each subject’s medical record that the subject and/or 
parent/guardian have a current unexpired epinephrine auto-injection device and have been 
trained in its proper usage including injection technique.  
5.9 
Symptomatic Treatment for Chronic and/or Recurrent Adverse Events 
Symptomatic treatment for chronic/recurrent AEs is permitted (except for 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 IgE-mediated AEs related to study product must be withdrawn by 4 weeks prior to the Exit 
DBPCFC.  
5.10 Prohibited Medications 
• 
Therapeutic immunomodulatory antibodies (eg, omalizumab, mepolizumab, 
reslizumab, etc.) 
• 
Systemic (oral) corticosteroids used for any duration greater than 3 consecutive 
weeks throughout the study. If used, subjects must not be up-dosed during the 3 days 
after ceasing the administration of oral steroids 
• 
Beta-blockers (oral) 
• 
Angiotensin-converting enzyme (ACE) inhibitors 
• 
Angiotensin-receptor blockers (ARB) 
• 
Calcium channel blockers 
• 
Tricyclic antidepressants 
During the course of the study, subjects may be at increased risk for anaphylaxis, which, in 
severe form, can result in a drop in blood pressure (BP). Additionally, the administration of 
epinephrine to treat anaphylaxis can result in a sudden rise in BP. For these reasons, the risks 
accompanying the use of any medication with known cardiovascular side effects must be 
weighed against the potential benefits of peanut OIT. This assessment must be performed for 
any medications being taken at study entry or added during the course of the study. The use 
of medication with known cardiovascular side effects during the course of the study is 
discouraged; 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 

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of this protocol to list all immunomodulatory drugs; broadly, these include drugs to treat or 
prevent transplant rejection, autoimmune disease, and certain neoplasias – examples include 
cyclosporine, tacrolimus, anti-tumor necrosis alpha drugs, and other anti-cytokine drugs. If 
an investigator contemplates the use of a potentially immunomodulatory drug during the 
course of the study, the investigator should discuss this with one of the study’s Medical 
Monitors.  
6 STUDY PROCEDURES 
6.1 
Enrollment and Randomization 
At ARC003 exit, subjects who have successfully completed the ARC003 study, signed 
ARC004 informed consent form (and assent, as age-appropriate), and satisfied all ARC004 
inclusion/exclusion criteria will be enrolled in ARC004. After obtaining signed ARC004 
consent (and assent as appropriate), screening procedures for ARC004 may be initiated. 
Screening procedures may be performed concurrently with the ARC003 Exit DBPCFC but 
must be completed prior to a subject’s enrollment in ARC004. Procedures that are performed 
as part of the ARC003 Exit Visit should not be repeated as part of the ARC004 Screening 
and Baseline Visit. Once the ARC003 Exit DBPCFC procedure is completed, subjects will 
be unblinded to their ARC003 treatment assignment and their treatment assignment will be 
verified against the ARC003 unblinded site records prior to enrollment in ARC004. Subjects 
will be assigned to Group 1 or Group 2 based on their treatment assignment in ARC003 
without re-randomization; Group 1 comprising those subjects who were assigned to placebo 
in ARC003, and Group 2 comprising those subjects who were assigned to active AR101 
treatment in ARC003. 
Subjects in Group 1, formerly receiving placebo in ARC003, must begin dosing in ARC004 
within 10 days of completion of ARC003. No subject in ARC004 should receive AR101 
administered on the same day as the ARC003 Exit DBPCFC. Subjects in Group 2 should 
begin dosing in ARC004 as soon as safe and feasible after their ARC003 Exit DBPCFC, and 
at maximum within 3 days of completing ARC003. For Group 2 subjects, this first dose can 
be given at home. If ARC004 dosing for a Group 2 subject does not commence within a 
3-day period of completing ARC003, the site should contact the Medical Monitor prior to 
administering the first dose.  
AR101 will be shipped directly to investigational sites and will be dispensed according to 
subject identification number, using a web-based interactive response system (IXRS). IXRS 
will also be used to randomize the Cohort 3 subjects into Cohort 3A, 3B, or 3C. 
6.2 
Screening and Baseline Visit – (Group 1 and Group 2) 
All screening procedures for the ARC004 Screening and Baseline Visit should be performed 
prior to entry in ARC004. Procedures that are performed as part of the ARC003 Exit Visit 
should not be repeated as part of the ARC004 Screening and Baseline Visit. Subjects should 

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not dose at home on the day of their ARC003 Exit Visit/ARC004 Screening and Baseline 
Visit if that visit includes a DBPCFC. The visit will include the following procedures: 
• 
ARC004 informed consent and assent, if not already performed. 
• 
Confirmation of treatment assignment from ARC003, following the completion of the 
ARC003 Exit DBPCFC. 
• 
Inclusion/exclusion criteria review. 
• 
Medical, allergy, and dietary history. 
• 
Concomitant medications. 
• 
Physical examination, including weight and height. 
• 
Serum pregnancy test for females of childbearing potential. 
• 
Pre-DBPCFC vital signs (BP, pulse rate [PR], body temperature). 
• 
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 (e.g., 
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. 
• 
DBPCFC (Part B of the Exit DBPCFC from ARC003). 
• 
Post-DBPCFC vital signs (BP, PR, body temperature). 
• 
Blood draw to collect samples for:  
– 
Peanut- and peanut component-specific IgE and IgG4 (immunoglobulin assays). 
The amount of blood to be taken for the immunoglobulin assays will be 
communicated from the central laboratory and included in the manual of 
procedures.  
– 
Complete blood cell count (CBC), obtained with the same venipuncture as the 
blood draw for the immunoglobulin assays.  
– 
Additional blood samples for optional exploratory immunologic studies. These 
can be obtained at selected centers with the same venipuncture as the blood draw 
for the immunoglobulin assays (separate informed consent required). 
• 
Optional collection of saliva sample for exploratory biomarker development at 
selected centers (separate informed consent required), as outlined in Appendix 6. Any 
subjects who consented to this optional substudy as part of ARC003, Amendment 3, 
will need to be re-consented to continue participating in ARC004.  
• 
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• 
Dispensing of investigational products for home dosing/return of unused 
investigational products. 
• 
Adverse event (AE) monitoring. 
• 
Asthma assessment by clinical history and Asthma Control Test, for those subjects 
with a clinical history of asthma. 
• 
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): 
– 
Recognition of an allergic reaction and of the symptoms of anaphylaxis 
– 
When and how to administer epinephrine via auto-injector 
– 
Requirement to go to nearest emergency facility following use of epinephrine 
auto-injector 
– 
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 
Study Visits 
The subsections that follow list the evaluations and procedures required at each study visit.  
Additionally, Appendix 1 contains the schedules of events for each treatment group as a 
reference guide.  To conserve space some visits are consolidated and some details omitted in 
the schedule of events.  For complete details on individual study visit requirements, please 
refer to the procedures specified in each subsection. 
6.3.1 
Initial Escalation: Day 1 (Group 1) 
The Initial Escalation Phase Visit for Group 1 subjects will occur within 10 days after the 
ARC003 Exit/ARC004 Screening and Baseline Visit. If the Initial Escalation is not started in 
this time frame, written approval to rescreen the subject and/or to waive any of the screening 
procedures must be obtained from the Sponsor’s Medical Monitor. 
A physician will be available at all times during the CRC peanut OIT 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 study product dose escalation. Additionally, 
subjects must be fully recovered (ie, back to their baseline state of health) from any 
preceding illness for ≥ 3 to 7 days, depending on the investigator-determined severity of the 
illness. 
The following assessments/procedures will be performed during the Initial Escalation Day 1 
visit in the CRC: 
• 
Concomitant medication update. 

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• 
Physical examination, including weight and height. 
• 
Diet (food allergen exposure) history update. 
• 
Pre-dose vital sign measurement (BP, PR, body temperature). 
• 
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* (FEV1), performed when PEFR shows a clinically relevant reduction or 
the subject shows clinical deterioration (e.g., 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. 
• 
Administration of AR101, with dosing beginning at 0.5 mg and progressing in 
graduated doses (if tolerated) of 1, 1.5, 3, and 6 mg. Following the first dose, 
subsequent doses will be delivered at 20 to 30 minute intervals. The schedule for 
initial day dose escalation is also shown in Table 1. 
• 
Post-dose vital sign measurements (BP, PR) within 15 to 30 minutes post-dose, and 
prior to next dose, and at 30-minute intervals thereafter, if the time between doses is 
extended, and for the duration of the post-dose observation period. 
• 
Monitoring for AEs, including allergic symptoms (see below and Section 6.5.3.1 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 (eg, Jell-O®) 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 (1½ hours) after completion of dose 
escalation, with vital sign measurements and assessment for signs and symptoms of allergic 
reaction performed every 30 minutes. Any signs or symptoms of allergic reaction will be 
recorded in the case report form (CRF) on the appropriate Dosing Symptom/AE form. 
If Day 1 dose escalation is completed with no symptoms detected after 1½ hours of post-dose 
observation following the last dose, the subject may be sent home from the CRC. If the 
subject exhibited mild symptoms, the duration of the observation period should be a 
minimum of 1 hour after resolution of the symptoms. For moderate symptoms, the 
observation period should be extended to a minimum of 2 hours after resolution of the 
symptoms. 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. 

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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. 
If dose-limiting symptoms occur at or before the 3-mg single dose, there will be no further 
dosing of study product, and the subject will be classified as an escalation failure and a 
nonresponder for the purpose of primary and key secondary analyses. The subject will be 
asked to return to the CRC 14 days following the last dose of study product to undergo an 
Early Discontinuation Visit (Section 6.3.10). Adverse events will be evaluated from the onset 
until the event is resolved or medically stable, or until 30 days after the Early Discontinuation 
Visit, whichever comes first. 
If no dose-limiting symptoms occur during Day 1 dose escalation, or if dose-limiting 
symptoms occur only with the 6-mg single dose, the subject is to return to the CRC on the 
following day, Day 2, to confirm the tolerability of a single 3 mg dose of AR101. 
6.3.2 
Initial Escalation: Day 2 (Group 1) 
On Day 2, the next consecutive day following Day 1, a single confirmatory 3-mg dose will 
be administered under medical supervision in the CRC. The only exception to Day 2 
immediately following Day 1 is when unforeseen circumstances (eg, an intercurrent illness) 
creates a safety risk to provide the next dose, consistent with the rules for missed doses 
(Section 6.6).  
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 during the Initial Escalation Day 2 
visit in the CRC: 
• 
Concomitant medication update. 
• 
Diet (food allergen exposure) history update. 
• 
Symptom-directed physical examination. 
• 
Pre-dose vital sign measurement (BP, PR, body temperature). 
• 
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* (FEV1), performed when PEFR shows a clinically relevant reduction or 
the subject shows clinical deterioration (e.g., active wheeze on physical examination); 
3 attempts of FEV1 should be performed, and the best attempt selected.  

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*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. 
• 
Oral administration of a single 3 mg dose of AR101. 
• 
Post-dose vital sign measurements (BP, PR) within 15 to 30 minutes post dose, prior 
to discharge, and as indicated per investigator discretion during the post-dose 
observation period. Subjects with moderate or severe symptoms should be monitored 
every 30 minutes.  
• 
Monitoring for AEs, including allergic symptoms (Section 7).  
• 
Diary review with subject. 
• 
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 1½ hours after dose administration, with vital 
sign measurements and assessment for signs and symptoms of allergic reaction performed 
every 30 minutes. Any signs or symptoms of allergic reaction will be recorded in the CRF on 
the appropriate Dosing Symptom/AE form. 
If Day 2 dosing is completed with no symptoms detected after 1½ hours 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 a minimum of 1 hour after 
resolution of the symptoms. For moderate symptoms, the observation period should be 
extended to a minimum of 2 hours after resolution of the symptoms. For severe symptoms, 
the subject should be observed for a minimum of 3 hours after resolution of the symptoms, 
either at the CRC or an emergency facility, as appropriate. 
Any subject deemed to have severe symptoms that include hypoxia, hypotension, or change 
in mental status (stage 3 anaphylaxis defined in Appendix 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 dose-limiting symptoms occur on Day 2, there will be no further dosing of AR101, and the 
subject will be classified as an escalation failure and a nonresponder for the purpose of 
primary and key secondary analyses. The subject will be asked to return to the CRC 14 days 
following the last dose of study product to undergo an Early Discontinuation Visit 
(Section 6.3.10). Adverse events will be evaluated from the onset until the event is resolved 
or medically stable, or until 30 days after the Early Discontinuation Visit, whichever comes 
first. 
Those subjects who tolerate the single 3 mg dose of study product on Day 2 will be 
dispensed a 2-week supply of study product at the 3 mg/d dose level. They will be instructed 
to continue daily oral dosing at home, starting the following day (Study Day 3), and to 
continue daily home dosing at that dose level for 2 weeks until next escalation. 

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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/Repeat Up-dosing Visits (Group 1 and Subjects Switching to Daily 
Dosing) 
6.3.3.1 
Group 1 Up-dosing 
The Up-dosing Period for Group 1 will last approximately 22 (to a maximum of 40) weeks 
and comprise 11 scheduled up-dosing visits, 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 study product 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 study product until their flare of asthma, atopic 
disease, or intercurrent illness has resolved. 
Subjects should withhold their daily home dose of study product on in-clinic dosing days, but 
should take all other prescribed medications as scheduled. 
The following assessments/procedures are scheduled for each up-dosing visit in the CRC 
(except the 80 mg up-dosing visit and end of up-dosing/maintenance visit 1, Section 6.3.4 
and Section 6.3.5): 
• 
Concomitant medication review. 
• 
Diet (food allergen exposure) history update. 
• 
Return unused capsules to the clinic at each visit. 
• 
Symptom-directed physical examination. 
• 
Pre-dose vital sign measurement (BP, PR, body temperature). 
• 
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* (FEV1), performed when PEFR shows a clinically relevant reduction or 
the subject shows clinical deterioration (e.g., active wheeze on physical examination); 
3 attempts of FEV1 should be performed, and the best attempt selected.  

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*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. 
• 
Study product administration under observation in the clinic. 
• 
Post-dose vital sign measurements (BP, PR) within 15 to 30 minutes post dose, prior 
to discharge, and at the investigator’s discretion during the post-dose observation 
period. 
• 
Take home capsules for daily dosing until next visit. 
• 
Monitoring for compliance. 
• 
Monitoring for AEs, including allergic symptoms (Section 7.2). 
• 
Diary review with subject. 
• 
Subjects will be reminded to continue to follow a peanut-avoidant diet for the 
duration of the study. 
• 
Optional saliva collection at selected centers (per the Schedule of Events in 
Appendix 6). 
At a minimum, subjects must be observed for 1½ hours after dose administration, with vital 
sign measurements and assessment for signs and symptoms of allergic reaction performed 
every 30 minutes. Any signs or symptoms of allergic reaction will be recorded in the CRF on 
the appropriate Dosing Symptom/AE form. 
If up-dosing is completed with no symptoms detected after 1½ hours 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 a minimum of 1 hour after 
resolution of the symptoms. For moderate symptoms, the observation period should be 
extended to a minimum of 2 hours after resolution of the symptoms. And for severe 
symptoms, the subject should be observed for a minimum of 3 hours after resolution of the 
symptoms, either at the CRC or an emergency facility, as appropriate. 
Any subject deemed to have severe symptoms that include hypoxia, hypotension, or change 
in mental status (stage 3 anaphylaxis defined in Appendix 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. Further, if an investigator suspects that a subject has not tolerated, or is not 
tolerating, his or her current dose level, the investigator should have the subject return to the 
clinic to determine whether a dose reduction is warranted, and if so, the magnitude of the 

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reduction. Guidelines for setting the new, lower, dose are outlined in Section 6.5.5 with the 
dose adjustment depending on the severity of the dose-related symptoms. 
Subjects who require dose reduction during a 2-week dosing period will have their escalation 
schedule reset, as necessary, to maintain the new dose level for a 2-week period prior to 
attempting to re-escalate. 
Following a dose reduction, it is advised that an escalation attempt be made by 4 weeks, 
unless escalation is to be delayed further due to administration of epinephrine, as defined in 
Section 6.5.6. Failure to successfully escalate after 3 consecutive attempts, with each attempt 
spaced ≥ 2 weeks apart, will result in the cessation of dosing and the subject being 
considered an escalation failure and nonresponder. The subject will be asked to return to the 
CRC 14 days following the last dose of study product to undergo an Early Discontinuation 
Visit (Section 6.3.10) and is to be followed for safety in the interim. 
6.3.3.2 
Repeat Up-dosing (Subjects Switching to Daily Dosing) 
Subjects who have the option to switch to AR101 daily in ARC008 may begin daily dosing 
and have visits in the Repeat Up-dosing Period in ARC004 if ARC008 is not yet available at 
the study site (Section 3). The procedures to be performed are the same as those listed in 
Section 6.3.3.1, except that the subjects will start the Repeat Up-dosing Period at 80, 120, or 
160 mg dose and escalate from there. Repeat Up-dosing may be up to a maximum of 
26 weeks.  
6.3.4 
80 mg Up-dosing Visit 
The first 80 mg in-clinic dosing visit is the approximate midpoint of the Up-dosing Period. 
At this visit the following procedures are to be performed in addition to those performed at 
the other up-dosing visits: 
• 
Complete (not just symptom-directed) physical examination, including height and 
weight. 
• 
Assessment of asthma control in asthmatic subjects using the Asthma Control Test 
questionnaire.  
• 
Urine pregnancy test, for females of childbearing potential. 
• 
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): 
– 
Recognition of an allergic reaction and of the symptoms of anaphylaxis 
– 
When and how to administer epinephrine via auto-injector 

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– 
Requirement to go to nearest emergency facility following use of epinephrine 
auto-injector 
– 
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) 
6.3.5 
End of Up-dosing Visit/Start of Maintenance (Group 1 and Subjects Switching 
to Daily Dosing) 
The end of the Up-dosing Period/Maintenance Visit 1 occurs after a subject has maintained 
the 300 mg dose for approximately 2 weeks. The subject then enters the Maintenance Period 
and remains in it, even if the dose is adjusted due to adverse events (AEs). At the End of 
Up-dosing Visit/Maintenance Visit 1, the following procedures are to be performed:  
• 
Concomitant medications. 
• 
Diet (food allergen) history.  
• 
Complete (not just symptom-directed) physical examination, including height and 
weight. 
• 
Vital signs (BP, PR, body temperature). 
• 
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* (FEV1), performed when PEFR shows a clinically relevant reduction or 
the subject shows clinical deterioration (e.g., 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. 
• 
Urine pregnancy test, for females of childbearing potential. 
• 
Blood draw to collect samples for:  
– 
Immunoglobulin assays (peanut-specific IgE, IgG4). The amount of blood to be 
taken for the immunoglobulin assays will be communicated from the central 
laboratory and included in the manual of procedures.  
– 
Complete blood count, obtained with the same venipuncture as the blood draw for 
the immunoglobulin assays. 
– 
Optional blood samples for exploratory immune studies at selected centers. Note 
that these samples can be obtained with the same venipuncture as the blood draw 
for the immunoglobulin assays and CBC, but will require an additional volume of 
blood to be collected. Separate informed consent is required.  

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– 
The amount of blood to be taken in total for the above assays (required 
immunoglobulin assays, required CBC, and optional exploratory immune studies 
sample) will not exceed a total volume of 0.67 mL/kg in children, to a maximum 
of 50 mL, total, in 8 weeks. Blood draw should be collected in compliance with 
local laboratory guidelines and testing regulations. 
• 
Optional saliva collection at selected centers (Appendix 6). 
• 
Skin prick test to peanut extract. 
• 
Administration of OIT at site. 
• 
Diary review with subject. 
• 
Dispense/ return unused study product. 
• 
Monitor AEs/allergic symptoms. 
• 
Monitor for compliance. 
• 
Assessment of asthma control in asthmatic subjects using the Asthma Control Test 
(ACT). 
• 
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): 
– 
Recognition of an allergic reaction and of the symptoms of anaphylaxis  
– 
When and how to administer epinephrine via auto-injector 
– 
Requirement to go to nearest emergency facility following use of epinephrine 
auto-injector 
– 
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)  
• 
Telephone follow-up. 
For the first 2-week dosing interval at the 300 mg/d maintenance dose, the dose will be 
administered from 300 mg capsules. Thereafter, 300 mg doses may be administered from 
foil-laminate sachets. 
6.3.6 
Maintenance Visits (Group 1 and Subjects Switching to Daily Dosing) 
The Maintenance Period begins approximately 2 weeks after the subject reaches the 300 mg 
in-clinic dosing visit. The first in-clinic visit in the Maintenance Period is to occur 
approximately 2 weeks after the start of dosing at 300 mg/d and is the End of Up-dosing 
Visit/Maintenance Visit 1. Thereafter, Maintenance Period visits will occur approximately 
every 12 weeks (e.g., Weeks 12 and 24) prior to the subject entering Extended Maintenance).  
Subjects should withhold their daily home dose of study product on in-clinic dosing days, but 
should take all other prescribed medications as scheduled.  

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The following assessments/procedures are scheduled for each in-clinic dosing Maintenance 
Visit in the CRC: 
• 
Concomitant medication review. 
• 
Diet (food allergen exposure) history update. 
• 
Return unused sachets or capsules to the clinic at each visit. 
• 
Symptom-directed physical examination. 
• 
Pre-dose vital sign measurement (BP, PR, body temperature). 
• 
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* (FEV1), performed when PEFR shows a clinically relevant reduction or 
the subject shows clinical deterioration (e.g., 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. 
• 
Assessment of asthma control in asthmatic subjects using the Asthma Control Test. 
• 
Study product administration under observation in the clinic. 
• 
Post-dose vital sign measurements (BP, PR) within 15 to 30 minutes post dose, and at 
15- to 30-minute intervals thereafter if the post-dose observation period is prolonged 
beyond the requisite 30 minutes (see below). 
• 
Take home sachets (or capsules, as appropriate) for daily dosing until next visit. 
• 
Monitoring for compliance.  
• 
Monitoring for AEs, including allergic symptoms (Section 7.2). 
• 
Diary review with subject. 
• 
Subjects will be reminded to continue to follow a peanut-avoidant diet for the 
duration of the study.  
• 
Telephone follow-up.   
In the event that dose reduction from the stable dose of 300 mg/d is required during the last 
weeks of the planned 24-week Maintenance Period, the Maintenance Period may be extended 
on an individual basis up to an additional 4 weeks (to a maximum of 28 weeks) or to a 
maximum study duration of 68 weeks, whichever is shorter. The Post-Maintenance DBPCFC 
must be performed in Group 1 subjects by Week 68.  
If dosing is discontinued, the subject will be asked to return to the CRC 14 days following 
their last dose of AR101 to undergo an Early Discontinuation Visit (Section 6.3.10). 

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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 6.5.3), except that the initial period of required post-dose 
observation may be shortened to 30 minutes for tolerated doses. 
Additional procedures are to be performed before the Post-Maintenance DBPCFC at the end 
of Initial Maintenance for group 1 subjects only, as follows:   
• 
Blood draw to collect samples for:  
– 
Immunoglobulin assays (peanut-specific IgE, IgG4). The amount of blood to be 
taken for the immunoglobulin assays will be communicated from the central 
laboratory and included in the manual of procedures.   
– 
CBC, obtained with the same venipuncture as the blood draw for the 
immunoglobulin assays.  
– 
Optional blood samples for exploratory immune studies at selected centers. Note 
that these samples can be obtained with the same venipuncture as the blood draw 
for the immunoglobulin assays and CBC, but will require an additional volume of 
blood to be collected. Separate informed consent is required.   
– 
The amount of blood to be taken in total for the above assays (required 
immunoglobulin assays, required CBC, and optional exploratory immune studies 
sample) will not exceed a total volume of 0.67 mL/kg in children, to a maximum 
of 50 mL, total, in 8 weeks. Blood draw should be collected in compliance with 
local laboratory guidelines and testing regulations.   
• 
Skin prick test to peanut extract.   
6.3.7 
Double-Blind, Placebo-Controlled Food Challenge (Groups 1 and 2) 
Group 1 subjects will undergo a Post-Maintenance DBPCFC, to be conducted in the same 
manner as the ARC003 Exit DBPCFC, but with a top dose of 2000 mg (4043 mg cumulative) 
peanut protein added, as shown in Table 4.  
All subjects in Groups 1 and 2 who complete their dosing regimen will undergo an Exit 
DBPCFC up to a single highest dose of 2000 mg of peanut protein (4043 mg cumulative), 
according to Table 4. For subjects who do not tolerate their nondaily dosing regimen and 
subjects who switch to daily dosing after missing their nondaily dose for > 3 days, the Exit 
DBPCFC will be omitted before discontinuation from ARC004 and enrollment in ARC008. 
Subjects should not administer their AR101 dose on the day of the DBPCFC.  All DBPCFCs 
will be conducted and evaluated based on PRACTALL guidelines. Sites will be provided a 
DBPFCFC manual, as in ARC003.  
6.3.8 
All Subjects (Groups 1 and 2): Extended Maintenance Visits 
The EM period begins upon entry in ARC004 for Group 2, and following completion of the 
Post-Maintenance DBPCFC for Group 1.  

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6.3.8.1 
Alternate Dosing Initiation Visit: Day 1  
Subjects in Cohorts 2, 3B, and 3C will change to BIW dosing once they have tolerated QOD 
dosing for 4 weeks. Subsequently Cohort 3C may extend the interval further. Subjects 
extending their dosing interval (eg, QOD to BIW, BIW to QW, QW, to QOW) will do so by 
taking the first 2 doses of the new interval under observation in clinic (except QOD). Every 
effort should be made to ensure the new interval is the appropriate interval. Some or all of the 
following procedures may be performed at the first of these 2 visits, according to the 
procedures outlined in the Schedule of Events: 
• 
Diet (food allergen) history. 
• 
Concomitant medication update. 
• 
Symptom-directed physical examination. 
• 
Pre-dose vital sign measurement (BP, PR, body temperature). 
• 
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* (FEV1), performed when PEFR shows a clinically relevant reduction or 
the subject shows clinical deterioration (e.g., 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. 
• 
Urine pregnancy test. 
• 
Oral administration of AR101. 
• 
Skin prick test. 
• 
Post-dose vital sign measurements (BP, PR) within 15 to 30 minutes post dose, prior 
to discharge, and as indicated per investigator discretion during the post-dose 
observation period. Subjects with moderate or severe symptoms should be monitored 
every 30 minutes.  
• 
Blood draw to collect samples for:  
– 
Immunoglobulin assays. The amount of blood taken for the immunoglobulin 
assays will be communicated from the central laboratory and included in the 
Manual of Procedures.  
– 
CBC, obtained with the same venipuncture as the blood draw for the 
immunoglobulin assays. 
– 
Optional blood draw for exploratory immune studies at selected centers. Note that 
these can be obtained with the same venipuncture as the blood draw for the 
immunoglobulin assays. Separate informed consent is required. 

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– 
The amount of blood to be taken for the above assays (required immunoglobulin 
assays, required CBC, and optional immune cell characterization assays) will not 
exceed a total volume of 0.67 mL/kg in children, to a maximum of 50 mL, total, 
in 8 weeks. Blood draw should be collected in compliance with local laboratory 
guidelines and testing regulations. 
• 
Monitoring for AEs, including allergic symptoms.  
• 
Monitoring for compliance. 
• 
Diary review with subject. 
• 
Subjects will be reminded to continue to follow a peanut-avoidant diet for the 
duration of the study. 
• 
Telephone follow-up.   
6.3.8.2 
Alternate Dosing Initiation Visit: Day 2  
Subjects in the cohorts listed above will return to take their second BIW, QW, or QOW dose 
under observation in clinic. Procedures performed on Day 2 are a subset of procedures 
performed on Day 1. The following will also occur at the Day 2 visit: Dispense study drug. 
6.3.9 
Follow-up Extended Maintenance Visits 
The follow-up EM period visits should take place approximately every 14 weeks and occur 
on a day when the dosing interval is due to be changed and/or the subject is due to take the 
previously specified dose.  
Subjects should withhold their daily home dose of study product on in-clinic dosing days, but 
should take all other prescribed medications as scheduled.  
Some or all of the following assessments/procedures are scheduled for in-clinic dosing EM 
period visits in the CRC, according to the Schedule of Events: 
• 
Concomitant medication review. 
• 
Diet (food allergen exposure) history update. 
• 
Return unused sachets or capsules to the clinic at each visit. 
• 
Symptom-directed physical examination. 
• 
Pre-dose vital sign measurement (BP, PR, body temperature). 
• 
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. 

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• 
Spirometry* (FEV1), performed when PEFR shows a clinically relevant reduction or 
the subject shows clinical deterioration (e.g., 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. 
• 
Assessment of asthma control in asthmatic subjects using the Asthma Control Test 
questionnaire. 
• 
Urine pregnancy test. 
• 
Skin prick test at entry into EM and every 28 weeks while on QD treatment; more 
frequently when on nondaily treatments as per the Schedules of Events (Appendix 1). 
• 
Blood draw to collect samples for:  
– 
Immunoglobulin assays. The amount of blood taken for the immunoglobulin 
assays will be communicated from the central laboratory and included in the 
Manual of Procedures.  
– 
CBC, obtained with the same venipuncture as the blood draw for the 
immunoglobulin assays. 
– 
Optional blood draw for exploratory immune studies at selected centers. Note that 
these can be obtained with the same venipuncture as the blood draw for the 
immunoglobulin assays. Separate informed consent is required. 
– 
The amount of blood to be taken for the above assays (required immunoglobulin 
assays, required CBC, and optional immune cell characterization assays) will not 
exceed a total volume of 0.67 mL/kg in children, to a maximum of 50 mL, total, 
in 8 weeks. Blood draw should be collected in compliance with local laboratory 
guidelines and testing regulations. 
• 
Study product administration under observation in the clinic. 
• 
Post-dose vital sign measurements (BP, PR) within 15 to 30 minutes post dose, and at 
15- to 30-minute intervals thereafter if the post-dose observation period is prolonged 
beyond the requisite 30 minutes (see below). 
• 
Take home sachets for daily dosing until next visit. 
• 
Monitoring for compliance.  
• 
Monitoring for AEs, including allergic symptoms (Section 7.2 and Section 4). 
• 
Subjects will be reminded to continue to follow a peanut-avoidant diet for the 
duration of the study and encouraged to call the site with any questions or concerns 
about the intermittent dosing schedule.  
The procedure for monitoring subjects for safety after in-clinic dosing is the same as for 
up-dosing visits (Section 6.5.3), except that the initial period of required post-dose 
observation may be shortened to 30 min for tolerated doses. 
If dosing is discontinued during the EM period, the subject will be asked to return to the CRC 
14 days following his or her last dose of AR101 to undergo an Early Discontinuation Visit 
(Section 6.3.10).  

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In addition to in-person clinic visits, sites will contact subjects by telephone periodically 
during EM to assess ongoing tolerability of doses, adherence to dosing schedule, and 
assessment of medical history/concomitant medications. All phone contacts are to be 
documented in the subject source record.  
6.3.10 Exit Visit/Early Discontinuation Visit 
Subjects who tolerate their EM regimen and complete the EM phase will have an Exit Visit, 
including an Exit DBPCFC, per Figure 1 and the Schedule of Events (Appendix 1).  
Subjects who fail initial escalation or up-dosing, or who prematurely discontinue treatment at 
any other time during the study, will return to the site for an Early Discontinuation Visit that 
consists of the same procedures as the Exit Visit, but without a DBPCFC. The Early 
Discontinuation Visit is to occur 14 days after the last dose of study product for those 
subjects who will permanently discontinue AR101 treatment.  
Subjects who have the option to switch to AR101 daily in ARC008 (Section 3) have 
2 options to continue, depending on whether ARC008 is available at their study site. If 
ARC008 is available, subjects will complete an ARC004 Early Discontinuation Visit without 
a DBPCFC and enroll in ARC008 where they will undergo Repeat Up-dosing. If ARC008 is 
not available at the study site, subjects may start AR101 daily dosing and have visits in 
ARC004 until ARC008 is available, then continue dosing in ARC008.  
Once ARC008 is available at the study site, subjects will have their Early Discontinuation 
Visit within 3 days following their last dose of AR101 in ARC004. The exit DBPCFC will be 
omitted.  
Subjects who withdraw from ARC004 wholly or in part due to intolerable GI symptoms, who 
are not enrolled in the optional saliva study, may be approached at the time of their Early 
Discontinuation Visit to provide voluntary consent to enroll and participate in the saliva 
sub-study. If this occurs, such subjects will provide a saliva sample as part of the Early 
Discontinuation Visit and then again during post-OIT follow-up (table in Appendix 6). 
The following procedures will be performed at the Exit/Early Discontinuation Visit: 
• 
Concomitant medication review. 
• 
Diet (food allergen) history.  
• 
Completion of the food allergy related quality of life questionnaire (FAQLQ), and the 
food allergy independent measure (FAIM) questionnaire after the completion of the 
Exit DBPCFC.  
• 
Completion of the Treatment Satisfaction Questionnaire for Medication (TSQM-9) 
and the exit questionnaire after the completion of the Exit DBPCFC.  
• 
Assessment of asthma control in asthmatic subjects using the Asthma Control Test 
questionnaire.  
• 
Complete (not just symptom-directed) physical examination, including height and 
weight. 

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• 
Vital signs (BP, PR, body temperature); if DBPCFC is to be conducted, these vital 
sign measurements should be taken shortly before the first challenge dose. 
• 
DBPCFC, for ARC004 completers.  
• 
Post-DBPCFC vital signs. 
• 
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* (FEV1), performed when PEFR shows a clinically relevant reduction or 
the subject shows clinical deterioration (e.g., 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. 
• 
Urine pregnancy test, for females of childbearing potential. 
• 
Blood draw to collect samples for:  
– 
Immunoglobulin assays. The amount of blood taken for the immunoglobulin 
assays will be communicated from the central laboratory and included in the 
Manual of Procedures.  
– 
CBC, obtained with the same venipuncture as the blood draw for the 
immunoglobulin assays. 
– 
Optional blood draw for exploratory immune studies at selected centers. Note that 
these can be obtained with the same venipuncture as the blood draw for the 
immunoglobulin assays. Separate informed consent is required. 
– 
The amount of blood to be taken for the above assays (required immunoglobulin 
assays, required CBC, and optional immune cell characterization assays) will not 
exceed a total volume of 0.67 mL/kg in children, to a maximum of 50 mL, total, 
in 8 weeks. Blood draw should be collected in compliance with local laboratory 
guidelines and testing regulations. (For subjects who are withdrawing prematurely 
from the study due to an AE, the blood draw at the Early Discontinuation Visit 
can be foregone if it was performed at the time that dosing with study product 
ceased.)  
• 
Skin prick test prior to Part A of the DBPCFC. 
• 
Monitoring for compliance. 
• 
Monitoring for AEs, including allergic symptoms (Section 6.5 and Section 7.2). 
• 
Diary review with subject. 
• 
Optional saliva collection (at selected centers) and PEESS v 2.0 questionnaire, as 
indicated (Appendix 6), for subjects terminating early where GI AEIs were a 
contributing factor (Section 7.3.3.2). 
• 
Reminder to continue peanut-avoidant diet. 

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• 
Return any unused AR101. 
• 
If the subject is at a study site that has not yet received approval to enroll subjects in 
ARC008, an additional 14-weeks supply of AR101 may be dispensed to the subject.  
The subject will return to the study site every 14 weeks for an Unscheduled Visit to 
obtain additional AR101 supplies and to ensure subject safety until such time that 
ARC008 is enrolling subjects at the site.  Once ARC008 is open to enrollment at the 
study site, the subject will return to clinic and complete the Early Discontinuation 
Visit to return any unused AR101. 
Eligible subjects at their Exit Visit will have an Exit DBPCFC performed. The Exit DBPCFC 
is to be conducted in accordance with PRACTALL guidelines, with the protocol-specified 
modifications, as described in Section 6.3.10. 
All ARC004 subjects who tolerate ≥ 443 mg cumulative peanut protein at the Exit DBPCFC 
are eligible to proceed to Study ARC008. Those on QD dosing at the end of EM who do not 
pass the Exit DBPCFC at ≥ 443 mg cumulative challenge dose level will be considered 
endpoint failures and nonresponders for the primary analysis. They will not be eligible for 
rollover into the ARC008 protocol due to safety concerns.  
However, subjects on a nondaily dosing regimen (QOD, BIW, QW, or QOW) who tolerate 
less than the 300 mg single dose of peanut protein (443 mg cumulative) at the Exit DBPCFC 
will not necessarily be excluded from ARC008, if otherwise eligible. If continued treatment 
with AR101 is determined to be safe per investigator judgment and after discussion with the 
medical monitor, these subjects will have the option to receive AR101 daily in ARC008. If 
ARC008 is not yet available or able to accept these subjects at the study site, these subjects 
may start AR101 daily dosing and have visits in ARC004 until they can enroll in ARC008.  
6.4 
Unscheduled Visits / Unscheduled Blood Draws 
The procedures performed at unscheduled visits may include any or all of those performed at 
Up-dosing, Initial Maintenance, or Extended Maintenance visits, as applicable. 
Additionally, if a subject (subject’s parent/guardian) declares his or her intention to 
discontinue study product dosing, whether at a scheduled visit or an unscheduled visit, a 
blood draw should be performed to obtain a CBC, immunoglobulin assays, and optional 
exploratory immune cell characterization samples (if the subject is participating in the 
substudy). If a blood draw is performed at this time, it will take the place of the Exit 
Visit/Early Discontinuation Visit blood draw (Section 6.3.10). 
6.5 
Assessment and Treatment of Allergic Reactions to Peanut OIT 
6.5.1 
Assessment of the Severity of Acute Allergic Reactions to Peanut OIT  
Subjects may develop allergic symptoms during the course of OIT, similar to those seen 
during other desensitization protocols (eg, venom immunotherapy, drug desensitization, 
desensitization to aeroallergens by subcutaneous injection). The severity of the reaction will 

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be determined based on 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 mild pruritus (eg, causing occasional scratching) 
• 
Respiratory – rhinorrhea (eg, occasional sniffling or sneezing), nasal congestion, 
occasional cough, throat discomfort  
• 
Gastrointestinal – mild abdominal discomfort (including mild nausea), minor 
vomiting (typically a single episode) and/or a single episode of diarrhea 
Moderate symptoms: 
• 
Skin – systemic hives (eg, numerous or widespread hives), swelling (eg, significant 
lip or face edema), pruritus causing protracted scratching, more than a few areas of 
erythema, or pronounced erythema  
• 
Respiratory – throat tightness without hoarseness, persistent cough, wheezing without 
dyspnea 
• 
Gastrointestinal – persistent moderate abdominal pain/cramping/nausea, more than a 
single episode of vomiting and/or diarrhea 
Severe symptoms: 
• 
Skin – severe generalized urticaria/angioedema/erythema  
• 
Respiratory – laryngeal edema, throat tightness with hoarseness, wheezing with 
dyspnea, stridor  
• 
Gastrointestinal – severe abdominal pain/cramping/repetitive vomiting and/or 
diarrhea 
• 
Neurological – change in mental status 
• 
Circulatory – clinically significant hypotension (Appendix 3) 
6.5.2 
Assessment of the Tolerability of an Individual Dose of Study Product 
Determination of the tolerability of any individual dose of study product should be based on 
an assessment of acute symptoms occurring in close temporal succession to dosing. 
In general, the severity of allergic symptoms elicited at a particular dose of study product will 
define the tolerability of that dose of study product. 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 5 illustrates the likely combinations of symptom severity and 
tolerability. 

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Table 5: Allergy Symptom Severity and Study Product Dose Tolerability 
Symptom Severity 
Assessed Tolerability 
None 
Tolerated 
Mild, oropharyngeal symptoms only 
Tolerated 
Mild, meeting pre-defined tolerability criteria (Section 6.5.1) 
Tolerated 
Mild, not meeting pre-defined tolerability criteria (Section 6.5.1) 
Not tolerated 
Moderate (except for rare exceptions, Section 6.5.1) 
Not tolerated 
Severe 
Not tolerated 
 
In general, the severity of an allergic reaction will correspond to the maximum severity of 
any of its symptoms. 
No symptoms: If a dose elicits no symptoms, the dose will be assessed as tolerated. 
Mild symptoms: When dosing with study product elicits an acute reaction characterized by 
the appearance of only a mild symptom or symptoms, the investigator will be required to 
assess whether the dose was or was not tolerated. The determination of tolerability must be 
made based on 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, most acute allergic responses to dosing that are 
characterized by mild symptoms would be anticipated to meet the above criteria. If, however, 
an allergic response to dosing is characterized by mild symptoms that do not meet all of the 
above criteria (eg, has mild symptoms occurring in 2 or more organ systems, requires 
treatment with 2 doses of antihistamine or 1 dose epinephrine, shows progression in severity 
or distribution over time, is protracted in duration, or includes objective wheezing), then even 
though the allergic symptoms may be mild, the dose should be assessed to be not tolerated. If 
a dose elicits mild symptoms that do not fit all of the above criteria and the dose is assessed 
to be tolerated, then a brief explanation as to why the dose was considered tolerated must be 
recorded in the CRF. 

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Moderate symptoms: In general, if a dose elicits moderate symptoms, the dose will be 
assessed as not tolerated. There may, however, be rare occasions when a dose eliciting 
moderate symptoms could be assessed as tolerated. Generally, this would only be the case for 
a transient, self-limited (requiring no intervention and resolving completely) symptom 
occurring in a single organ system. In addition, typically the symptom would be subjective 
only. Any dose associated with moderate symptoms and assessed as tolerated must be 
accompanied by a brief explanation in the CRF as to why the dose was considered tolerated.  
Severe symptoms: If a dose elicits severe symptoms, the dose will be assessed as not 
tolerated. Whenever a dose elicits an allergic response characterized by 1 or more severe 
symptoms, the crucial decision, after adequate treatment for the allergic reaction has been 
administered, will be to determine whether the subject should continue in the study, dosing at 
a reduced dose level, or be discontinued early from the study. Please refer to individual 
stopping rules in Section 7.8.2. 
The determination of tolerability will decide the course of action to be taken in response to 
dose-related reactions (Section 6.5.3). 
6.5.3 
Assessment of the Tolerability of a Dose Level 
6.5.3.1 
Assessment of Acute Symptoms Occurring After Dosing 
The assessment of the tolerability of a single dose forms the foundation for assessing the 
tolerability of a dose level during home dosing when acute symptoms arise in close temporal 
succession to dosing. With the report of moderate or severe symptoms occurring during 
home-dosing, the dose level should be considered to be not tolerated and the subject brought 
to the clinic the day after the emergence of such symptoms for administration of the next 
dose of study product under medical supervision. If a dose administered at home is suspected 
not to have been tolerated, even based on mild symptoms, the subject should also return to 
the CRC for dosing under medical supervision at the time of the next scheduled dose.  
The recurrence of a mild symptom or symptoms over the course of several days of 
home-dosing should suggest that the dose level is not tolerated, even if each individual 
occurrence of symptoms could be assessed as tolerated based on the criteria listed above. If 
the investigational site is notified of mild dose-related symptoms on 4 or more occasions 
during a single week during QD dosing, the subject should be brought to the CRC for dosing 
under direct observation for assessment of the tolerability of the dose level. If mild 
dose-related symptoms are noted on 7 or more occasions during a 2-week dosing interval at a 
given dose level on QD dosing, that dose level should be considered not tolerated and 
appropriate action taken (Section 6.5.5.2). Such dose level reductions for chronic/recurrent 
symptoms are not permitted when subjects are on QOD, BIW, QW, or QOW treatment, and 
consideration should be given to withdrawing such subjects from the trial and enrolling them 
in ARC008. If ARC008 is not available at the time this determination is made, these subjects 
should undergo AR101 daily dosing and visits in ARC004, until ARC008 is available.  
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 

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under direct observation whenever acute allergic symptoms associated with dosing are 
reported.  
6.5.3.2 
Assessment of Chronic/Recurrent Symptoms  
Gastrointestinal symptoms were the most common potentially allergic symptoms to occur on 
a subacute, chronic, and/or recurrent basis during Phase 2 clinical trials with AR101. Atopic 
dermatitis, seasonal allergies, or asthma are other potentially non-acute allergic reactions that 
could be brought on or exacerbated by OIT. The absence of a clear temporal relationship 
between dosing and the emergence of recurrent symptoms may help to distinguish these from 
acute dosing-related symptoms.  
If symptoms arise that suggest a chronic/recurrent reaction to study product in a daily dosing 
regimen, the dose level should be reduced. As with acute symptoms, the level of the dose 
reduction should be guided by the severity of the symptoms. Symptomatic treatment is 
permitted (Section 6.5.5), 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. When 
dose interruptions occur due to GI AEs, the subject should fill out a PEESS v 2.0 
questionnaire as soon as possible (Section 7.3.3.2). Voluntary saliva collection should also 
ensue as per Appendix 6 for all subjects consented into this additional study. Any subject 
who has not consented for participation into the voluntary saliva study, and who experiences 
GI AEs that interrupt dosing, may be approached to provide consent and donate saliva at the 
time of their dosing interruption and/or withdrawal.  
For Group 1 subjects determined to be having dose-limiting chronic/recurrent GI symptoms 
during Up-dosing, at up to and including the 20 mg/d dose level, it is advised that dosing of 
study product 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 6.6). 
For subjects who develop dose-limiting chronic/recurrent GI symptoms at the 40 mg/d dose 
level or above, dose reduction and re-escalation is to proceed as described in Section 6.5.5. 
6.5.4 
Treatment of Acute Reactions to Peanut OIT during Initial Escalation 
(Group 1) 
The algorithm for managing acute allergic symptoms during OIT during the Initial 
Escalation, Day 1 (Group 1), is shown in Figure 2. Explanatory text follows the figure.  

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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 
• 
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 clinical discretion). 

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For other mild symptoms, the action to be taken, at the investigator’s discretion, 
should be to either:  
– 
Advance to next dose in 30 to 60 minutes, or 
– 
Treat with antihistamine and then resume dose escalation within 60 minutes of 
last dose, provided that symptoms have resolved to the point where the 
investigator assesses the subject to be safe to continue dosing (ie, having no or 
only minimal residual signs or symptoms) 
– 
In general, if a subject requires only 1 or 2 doses of an 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 and the subject considered an escalation failure and desensitization 
nonresponder.  
– 
The decision to discontinue escalation is to be based solely on the determination 
of whether the allergic reaction was of moderate severity.  
– 
Although it is generally the case that some form of treatment will be instituted for 
moderate symptoms, treatment is not a requirement for assessing an allergic 
reaction as being of moderate severity.  
• 
Severe symptoms: For severe symptoms, the actions taken should be to discontinue 
the initial escalation and administer the appropriate rescue medications. The 
desensitization procedure will be discontinued regardless of the dose at which the 
severe symptom or symptoms occurred, and the subject will be considered an 
escalation failure and desensitization nonresponder. 

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6.5.5 
Treatment for Reactions During the Up-dosing Period (Group 1): 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 discretion and are considered in greater 
detail in subsequent sections (Section 6.5.5.1, Section 6.5.5.2, Section 6.5.5.3, and Figure 2). 
• 
Dosing the subject under medical supervision in the CRC – this is encouraged 
whenever there is question as to the tolerability of a dose level. It may be performed 
at the current dose level or at a reduced dose level, if there is already a high index of 
suspicion that the current dose level has not been tolerated.  
• 
Holding dose level at current level for an additional 1 to 2 weeks before attempting 
dose escalation – this may be done at the discretion of the investigator if there is 
concern that the current dose level has not been sufficiently well tolerated to attempt 
up-doing to the next dose level.  
• 
Reducing dose by 1 or 2 dose levels and maintaining the reduced dose level for 
2- to 4-week period before attempting dose re-escalation – Generally, this should be 
the action taken when a dose that has been observed in the CRC is assessed as not 
tolerated, if a dose elicits moderately severe symptoms, if a single dose of 
epinephrine has been administered to treat a dosing reaction, 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 study product 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 study product 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 study product 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 study product depends on 
the duration for which dosing was withheld.  
• 
Reducing dose by 2 dose levels and maintaining the reduced dose level for ≥ 6 weeks 
– continuing dosing at a reduced dose level for ≥ 6 weeks prior to attempting 
re-escalation is mandatory if 2 doses of epinephrine are given to treat a single AE. 
• 
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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6.5.5.1 
Reactions to In-Clinic Dosing (Group 1) 
6.5.5.1.1 
Up-dosing Tolerated at First Dose at New Dose Level 
The scenarios listed below describe a subject considered to have tolerated the first dose at a 
new dose level. The procedures outlined for each scenario should be followed.  
• 
No symptoms: If a subject undergoes up-dosing 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 only: If the subject experiences oral/pharyngeal pruritus 
only 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 indicative of lack of tolerability begin to develop. 
• 
Mild symptoms, tolerated at first dose at new dose level (see Section 6.5.1 for 
definitions of mild symptoms): 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 that dose level for the requisite 2 weeks and 
return to the CRC for up-dosing at the next scheduled visit. If the dose again causes 
mild symptoms, but is assessed as tolerated, the subject may continue at that dose 
level or return to the last tolerated dose (at the investigator’s discretion) and continue 
dosing at home for the next 2 weeks at the investigator-determined dose level. (See 
Section 6.5.5.2 for actions to be taken in the event that symptoms develop during 
home-dosing.) If, following the first dose at a new dose level, the second dose at the 
new (increased) dose level is again accompanied by mild symptoms, but is assessed 
as not tolerated, the procedures outlined in the paragraph above should be followed. 
The algorithm for management of dose adjustments due to poorly tolerated doses is 
depicted in Figure 3. Explanatory text follows the figure. 

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Figure 3: Schematic for Management of Dose Adjustments due to Poorly Tolerated 
Doses (Groups 1 and 2) 
 
 
• 
Mild symptoms that indicate uncertainty regarding tolerability: If mild symptoms (see 
Section 6.5.1 for definitions of mild symptoms), other than oral/pharyngeal pruritus 
occur with the first dose at a new dose level and there is uncertainty about whether 
the dose is tolerated, 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 should 
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. 
• 
Mild symptoms that indicate lack of tolerability: If mild symptoms other than 
oral/pharyngeal pruritus 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).  

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If the reduced dose is assessed as tolerated, the subject is to continue that daily home 
dose for the ensuing 2 weeks. (See Section 6.5.5.2 for actions to be taken in the event 
that symptoms develop during home-dosing.) If the reduced dose is again assessed as 
not tolerated, the subject is to return to the CRC the next day for supervised dosing at 
a 1- or 2-step reduction in dose (per investigator judgment, based on severity of 
reaction). If this further reduced dose is assessed as tolerated, the subject will 
continue at that dose level for daily home-dosing over the ensuing 2 weeks. If, 
however, the reduced dose is assessed as not tolerated, the subject is to be considered 
an escalation failure non-responder. 
• 
Moderate symptoms occurring with a new dose level would indicate lack of 
tolerability, with rare exceptions. Exceptions would generally be for a transient, 
self-limited (requiring no intervention and resolving completely) symptom of 
moderate intensity occurring in a single organ system. In addition, the symptom 
would typically be subjective. 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; (see Section 6.5.2, for moderate symptoms 
assessed as tolerated). If moderate symptoms occur with the first dose at a new dose 
level, except for rare instances described above, 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 that 
daily home dose level for an additional 2 weeks.  
If the subject experiences mild symptoms at the reduced dose, the procedures for 
responding to a dose with mild symptoms should be followed (see above). If the 
subject experiences moderate symptoms at the reduced dose level, the subject should 
return to the CRC the next day and receive a further 1- or 2-step dose reduction (per 
investigator judgment). If this reduced dose is well tolerated, it will be continued as 
the daily home dose for ≥ 2 weeks before re-escalation is attempted in the CRC. If the 
dose is not well tolerated, but elicits mild symptoms, then the treatment procedures 
for responding to mild symptoms should be followed (see above). If, however, the 
subject again experiences moderate symptoms at the reduced dose level, a discussion 
with the Medical Monitor is to ensue to reach a decision as to whether to continue the 
subject in the study.  
In the rare instance that a dose eliciting moderate symptoms is assessed as tolerated, 
then the actions taken should be the same as for a dose with mild symptoms assessed 
as tolerated. 
• 
Severe symptoms (these always indicate lack of tolerability): 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 ≥ 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. 

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Severe symptoms requiring 0 to 1 dose of epinephrine: If a subject experiences severe 
symptoms requiring 0 to 1 dose of epinephrine, the procedure is to have the subject 
return to the CRC for the next dose and to reduce the dose by 2 dose levels. If no or 
mild symptoms (assessed as tolerable) occur, dosing may proceed at the reduced level 
for at least 2 and up to 4 weeks. If moderate or severe symptoms occur, dosing is to 
be discontinued.  
Severe symptoms requiring 2 doses of epinephrine: If a subject experiences severe 
symptoms requiring 2 doses of epinephrine, the procedures outlined in the above 
paragraph should be followed; however, dosing will proceed at the reduced dose level 
(if tolerated) for at least 6 and up to 8 weeks. 
For specific questions related to dose-escalation or continuation of the same dose that 
are not answered in the above protocol, the Medical Monitor will be available for 
consultation.  
6.5.5.1.2 
Up-dosing: Tolerability Uncertain or No Tolerability at First Dose at New 
Dose Level 
If a subject has symptoms in the CRC after up-dosing that suggest the dose was not tolerated, 
or suggest that tolerability of the dose is uncertain, the investigator must assess the 
tolerability, as outlined in Section 6.5.3. The algorithm for management of dose adjustments 
due to poorly tolerated doses is depicted in Figure 3. Explanatory text follows the figure.  
6.5.5.2 
Reactions to Dosing at Home (Groups 1 and 2) 
With the occurrence of symptoms of an acute reaction to study product after home-dosing, or 
any acute allergic reaction, subjects/parents or guardians are instructed to call the study site. 
The investigator must then determine whether or not the dose was tolerated (Section 6.5.3). 
Because of the reduced reliability inherent in the second-hand reporting of symptoms, 
investigators are strongly encouraged to have subjects return to the clinic to undergo dosing 
under direct observation whenever acute allergic symptoms associated with dosing are 
reported.  
When symptoms of a dose-related allergic reaction are reported during the course of daily 
home-dosing, the investigator must assess the severity of the reaction and whether the dose 
associated with the reaction was tolerated. The appropriate intervention will depend on the 
type and severity of symptoms (Section 6.5.5).  
In general, moderate or severe symptoms will be considered clinically significant, and any 
dose eliciting such symptoms assessed as not tolerated; however, mild symptoms may also 
be considered clinically significant (eg, if affecting multiple organ systems, increasing in 
intensity, occurring with increasing frequency, or affecting a larger area over time), and 
assessed as not tolerated. Whenever there is question as to the clinical significance of mild 
signs or symptoms, the investigator should have the subject return to the CRC for observed 
dosing under medical supervision.  

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For home-doses assessed as not tolerated based on acute dose-related symptoms, the same 
procedures described in Section 6.5.5  for adjusting up-dosing should be followed.  
The recurrence of mild symptoms over the course of several days of home-dosing should 
suggest that the dose level is not tolerated, even if each individual occurrence of symptoms 
could be assessed as tolerated based on 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 6.5.5.2 above. 
• 
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, 
as described in Section 6.5.3.2. 
• 
Discontinuation of dosing. 
Any subject who discontinues up-dosing due to severe or repeated allergic reactions to study 
product should have his/her mechanistic blood draw and CBC (Section 6.4) at, or as soon as 
possible to, the time of the last dose and no later than at his or her Early Discontinuation 
Visit. 
Home dosing symptoms during nondaily EM regimens are handled separately and discussed 
further in Section 6.5.7.  
6.5.5.3 
Dose Adjustment in Response to Intercurrent Adverse Events (QD Regimens 
only) 
At the investigating physician’s discretion, temporary dose reductions, ranging from a 1-step 
reduction (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 study product during menses 
is discerned, then a temporary dose reduction can be instituted during this time. A schematic 
showing procedures for temporary dose reductions due to intercurrent AEs is 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 (QD Regimens Only) 
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.
 
CRC = clinical research unit; QD = daily. 
 
• 
For dose reductions of ≤ 4 consecutive days, whether dose re-escalation is to occur at 
home or in the CRC is at the investigator’s discretion. If the reduction in dose is 
maintained for ≤ 4 consecutive days, then the pre-reduction dose level may be 
resumed, with the biweekly escalation schedule kept unaltered.  
• 
If a reduction in dose is maintained for 5 to 7 consecutive days, then the subject is to 
return to the CRC to undergo dosing under medical supervision. At the investigator’s 
discretion, the pre-reduction dose level may be resumed or dosing may continue at the 
reduced dose level. The biweekly escalation should be reset so that the subject 
receives ≥ 2 consecutive weeks of treatment at the dose level assigned (either the 
reduced or the pre-reduction dose level). 
• 
If a reduction in dose is maintained for 8 to 14 consecutive days, then the next 
escalation attempted must be conducted in the clinic, and it should only be to 1 dose 
level above the reduced dose. If the escalation is successful, the subject should 
continue home-dosing for a minimum of 2 weeks, with his or her biweekly escalation 
schedule reset as necessary.  
Doses of study product 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 6.6). 

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6.5.6 
Treatment for Reactions During the Up-dosing Period: Pharmacological and 
Supportive Treatments 
The treatment(s) for types of reactions during the Up-dosing period are summarized by 
severity of reaction in Table 6. 
Table 6: 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  
Antihistamines and/or epinephrine, as indicated 
Assessment of severity of reaction is described in Section 6.5.1. Assessment of tolerability of an 
individual dose is described in Section 6.5.2. 
 
• 
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 glucocorticosteroids, 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. If 
severe symptoms that qualify as stage 3 anaphylaxis (as defined in Appendix 3) occur 
at any time, dosing with study product will stop and the subject will be discontinued 
from the study as an escalation failure nonresponder.  
The procedures(s) that should be implemented after treatment of a reaction experienced 
during the Up-dosing period are summarized in Table 7. An explanation follows the table. 

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Table 7: Procedure(s) Following Treatment of a Reaction Experienced during the 
Up-dosing Period  
Treatment Given for Reaction 
Procedure(s) Following Treatment 
Antihistamines only  
• Continue dose escalation 
Epinephrine:  ≥2 doses taken either in CRC or at 
home 
• Discontinue dosing  
• Subject returns to CRC 14 days after last dose 
for Early Discontinuation Visit 
Epinephrine: single dose given in CRC 
• Stop dosing at CRC 
• Reduce next dose by 2 doses, both to be 
administered at CRC 
• Continue bi-weekly escalation  
Epinephrine required for a second consecutive time 
during, or after, 1 escalation attempt 
• Dose reduced by 2 dose levels. 
• Reduced dose level continued for 6 to 8 weeks 
• Escalation may be attempted after 6 to 8 weeks 
Epinephrine required for a third consecutive time 
during an escalation attempt 
• Discontinue dosing  
• Subject returns to CRC 14 days after last dose 
for Early Discontinuation Visit 
Epinephrine: single dose at home 
• Not counted in the total count of epinephrine 
uses unless severe anaphylaxis has occurred 
• Subject returns to CRC for an observed dose 
under medical supervision prior to resuming any 
dosing at home 
CRC = clinical research center. 
 
• 
Antihistamines  
If a subject receives antihistamines only, the dose escalation can be continued. If 
epinephrine is administered, then a different course of action is to be taken (see 
below).  
• 
Epinephrine – General Procedures 
Any reaction to study product (in clinic or at home) that requires more than 2 doses of 
epinephrine will halt all further dosing of study product for the individual. The 
subject will be asked to return to the CRC 14 days following the last dose of study 
product to undergo an Early Discontinuation Visit (Section 6.3.10). 
• 
Epinephrine – Single Dose Administered at Clinic 
If a single administration of epinephrine is required during or after a dose-escalation 
in the clinic, no further dosing of study product is to occur at that visit. The next dose 
of study product is to be reduced by 2 dose levels and administered in the CRC, but 
biweekly dose escalation should continue. 
If a single administration of epinephrine is required for a second consecutive time 
during, or after, 1 escalation attempt, the dose should be reduced by 2 dose levels, and 
the subject continued at that dose level for 6 to 8 weeks. After 6 to 8 weeks at the 
reduced dose, an escalation attempt may be tried in clinic. 

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If a single administration of epinephrine is required for a third consecutive time 
during an escalation attempt, no further dosing should be attempted. Dosing in these 
subjects will be discontinued. They will be asked to return to the CRC 14 days 
following their last dose of study product to undergo an Early Discontinuation Visit 
(Section 6.3.10). 
• 
Epinephrine – Home 
If a single administration of epinephrine is given during dosing at home, this 
epinephrine use is not counted as one of the uses described above, unless severe 
anaphylaxis is assessed to have occurred at home. Administration of epinephrine 
outside of the clinic should be followed immediately by the subject being taken to the 
nearest emergency department. The subject should return to clinic for an observed 
dose under medical supervision prior to resuming any dosing at home. 
6.5.7 
Reactions Occurring During the Maintenance and Extended Maintenance 
Periods (Groups 1 and 2) 
Dosing guidelines following treatments given for reactions experienced by subjects in 
Groups 1 and 2 receiving AR101 at 300 mg QD, QOD, BIW, QW, or QOW during the 
Maintenance and Extended Maintenance period are summarized in Table 8. A textual 
explanation follows the table. 
Table 8: Dosing Guidelines Following Treatment for Reactions Experienced by 
Subjects in Groups 1 and 2 Receiving AR101 at 300 mg QD, QOD, BIW, 
QW, or QOW During Maintenance and Extended Maintenance  
Treatment Regimen 
Dosing Guidelines and Procedures 
QD  
Follow Up-dosing procedures.  
QOD, BIW, QW, or QOW 
• Withhold the scheduled dose until the AE is 
resolved and the dose can be safely 
administered. 
• Reset the interval between doses after the 
subsequent dose is tolerated. 
– If the dose must be withheld for > 3 days 
past when the dose was due to be taken, the 
investigator must discuss the case with the 
Sponsor’s Medical Monitor prior to 
administering the next dose. Dosing options 
are described in the text following this 
table. 
BIW = twice weekly; QD = once daily; QOW = every other week; QW = once weekly. 
 
• 
This phase consists of the subject receiving the 300-mg dose of study product either 
QD, QOD, BIW, QW, or QOW. For any symptoms noted during the QD 
Maintenance or EM period, the same study product dosing guidelines and procedures 

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for QD dosing will be followed as for the Up-dosing Period. However, for subjects on 
nondaily regimens, the following guidelines and procedures apply:  
– 
The tolerability of doses on nondaily dosing regimens will be evaluated as in 
Section 6.5.2, keeping in mind the individual stopping rules related to tolerability 
and symptom severity as outlined in Section 7.8.2.  
– 
In the event of a clinically significant intercurrent AE occurring at the time of a 
scheduled QOD, BIW, QW, or QOW dose, subjects should be advised to 
withhold the scheduled dose until the AE is resolved and the dose can be safely 
administered; the interval between doses should be reset once the subsequent dose 
is tolerated.  
– 
If the dose must be withheld for > 3 days past when the dose was due to be taken, 
the investigator must discuss the case with the Sponsor’s Medical Monitor prior to 
administering the next dose. Options available at that time include, but are not 
limited to, any of the following: 
1. Continue ARC004 and administer the next 300 mg dose under supervision at 
the CRC. 
 
If tolerated, continue EM dosing at 300 mg on the same schedule, resetting 
the dosing interval;  
 
If not tolerated, consider options 2 or 3 below. 
2. Continue ARC004 and administer approximately half of the 300 mg dose 
under supervision at the CRC. The entire 300 mg dose should be prepared 
with the preferred vehicle and then approximately half of the dose should be 
administered; the remainder should be discarded. If not tolerated, the subject 
should be discontinued from the study. If tolerated, up to 3 successive doses 
can be administered this way according to the subject’s assigned schedule, but 
then 300 mg should again be attempted.  
3. Discontinue the subject from ARC004 and consider enrollment in ARC008 if 
the site has received approval to enroll subjects in ARC008. This should be 
the preferred option for any subject on a QOD, BIW, or QW dosing regimen 
whose interval between AR101 doses exceeds 14 days. If the subject is at a 
site that has not yet received approval to enroll subjects in ARC008, the 
subject may start AR101 daily dosing and have visits in the Repeat Up-dosing 
Period in ARC004 until ARC008 is available. 
• 
For subjects having acute reactions to QOD, BIW, QW, or QOW doses, appropriate 
treatment and follow-up is to be administered per Section 6.5.6. As mentioned in 
Section 7.8.2, any EM subject on QOD, BIW, QW, or QOW dosing having 1 related 
SAE; 1 related AE graded severe; 2 related AEs occurring on separate occasions, both 
graded moderate; or 3 consecutive doses judged “not tolerated,” will be considered as 
a treatment failure and discontinued from ARC004 for safety reasons. Such subjects 
may be eligible to enroll in ARC008 and return to a QD regimen. If a site has not yet 
received approval for enrollment of subjects in ARC008, the subjects may start 
AR101 daily dosing and have visits in ARC004 until ARC008 is available, then 
continue dosing in ARC008.   

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• 
Sites will ensure that all subjects have in-date epinephrine autoinjectors, appropriate 
anaphylaxis teaching, and access to emergency services as per local standards.  
6.6 
Missed Peanut OIT (Study Product) Doses during Up-dosing (Group 1) 
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. 
Figure 5: Procedures Following Missed Consecutive Doses of Peanut OIT 
Miss 1 to 2 doses in a row
• Next dose: current dose, which   
may be given at home
Miss 3 to 4 doses
Miss 5 to 6 doses in a row
• Miss  7 consecutive days of dosing 
due to non-compliance (vs. due to AE)
• Miss 3 consecutive days of dosing on 
3 occasions (considered excessive 
missed dosing)
• QD dosing regimen withheld for ≥15  
consecutive days for any reason
• Next dose: currently 
administered dose 
administered at the CRC only
• Next dose: ~50% of last 
tolerated dose, administered at 
the CRC
• Escalation: 1 dose level weekly 
(no less frequently than every 
4 weeks) until subject is 
returned to dose level
• Discontinue dosing
• Subject returns to CRC 14 
days after last dose for Early 
Discontinuation Visit
 
AE = adverse event; CRC = clinical research unit; OI = oral immunotherapy (ie, AR101 or study 
treatment). 
 
• 
Miss 1-2 doses in a row – The next dose would be the current dose level and could be 
given at home 
• 
Miss 3-4 doses in a row – The next dose would be the current dose and would be 
given under supervision in the CRC 
• 
Miss 5-6 doses in a row – 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 

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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 a study product dispensing error), constitutes an 
individual stopping rule and the subject is to stop taking study product. The subject 
will be considered an escalation failure nonresponder, and will be asked to return to 
the CRC 14 days following their last dose of study product to undergo an Early 
Discontinuation Visit (Section 6.3.10). 
• 
Additionally, excessive missed dosing, defined as 3 consecutive days of missed doses 
on 3 occasions during the Up-dosing Period, for any reason other than treatment of an 
AE, constitutes an individual stopping rule and the subject is to stop taking study 
product. The subject will be considered an escalation failure nonresponder, and will 
be asked to return to the CRC 14 days following their last dose of study product to 
undergo an Early Discontinuation Visit (Section 6.3.10). 
• 
If study product has been withheld for 8 to 14 consecutive days as treatment for an 
AE or due to a study product 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, 
(see Figure 6) 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. 
Figure 6: Procedures for Doses Withheld for 8 to 14 Days During the Maintenance 
Period 
OIT (AR101, study product) 
withheld for 8 to 14 consecutive 
days
• Next dose: ~50% of last 
tolerated dose.
• Escalation: 1 dose level weekly 
(no less frequently than every 
4 weeks) until subject returns 
to dose level. 
 
OIT = oral immunotherapy (ie, AR101, study product). 
 
• 
If a subject on a QD dosing regimen has his/her study product withheld for 
≥ 15 consecutive days for any reason, at any point in the study (with the exception of 
a dosing hiatus instituted for chronic/recurrent GI AEs at or before the 20 mg dose 
level, as per Section 6.5.3.2), the subject will be considered an escalation failure 
nonresponder, and will be asked to return to the CRC 14 days following their last 
dose of study product to undergo an Early Discontinuation Visit (Section 6.3.10). 

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During up-dosing, no attempt should be made to make up for a missed dose if greater than 
6 hours have elapsed since usual time of dosing. 
6.7 
Skin Prick Test 
Subjects will have SPTs performed using study-approved procedures for food allergens. 
After the subject is off antihistamines for an appropriate length of time (5 half-lives of the 
antihistamine that is being used), a skin test probe is pressed through a commercial extract of 
an allergen into the epidermis. Positive (histamine) and negative (saline-glycerin) controls 
are placed to establish that the response is not blocked and to determine if there is 
dermatographism, respectively. 
6.8 
Visit Windows 
Strict adherence to the dosing schedule should be maintained: 
• 
Study visits should occur within a ± 2-day window of the scheduled visit date (ie, 
2 days before or 2 days after the scheduled visit date) for all phases of the study until 
Week 14 of the EM phase. 
• 
Starting at Week 14 of the EM phase, the permissible window around study visits will 
be extended to 1 week before or 1 week after a planned in-clinic dosing visit (ie, ± 1 
week). 
• 
The Early Discontinuation Visit is to occur 14 days after the last dose of AR101. 
The permissible window is minus 3 days to plus 7 days for those subjects who will 
permanently discontinue AR101 treatment. 
• 
Study visits for scheduled blood draws or DBPCFC should take place within 2 weeks 
of the scheduled visit. 
6.9 
Other Safety Assessments 
6.9.1 
Physical Examination and Vital Signs 
Physical examinations will be conducted at visits indicated in the Schedules of Events 
(Appendix 1). Height and weight will also be recorded. Vital signs will also be assessed, 
including BP, PR, and body temperature. 
6.9.2 
Prior and Concomitant Medications 
Prior and concomitant medications will be documented in the CRF. 
6.9.3 
Pregnancy Test 
All female subjects of child-bearing potential will undergo serum pregnancy testing at 
baseline and then routine urine pregnancy testing throughout the study at the visits indicated 
per protocol (Section 6.3). 

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7 SAFETY MONITORING 
This section defines the types of safety events that should be reported and outlines the 
procedures for appropriately collecting, grading, recording, and reporting them. A Safety 
Monitoring Committee (SMC) will be established to monitor study safety events and will 
meet approximately quarterly throughout the study. 
7.1 
Definitions 
All safety events observed under this protocol are reported through the electronic data 
capture (EDC) system for the duration of the study. Some safety events arising under certain 
defined conditions are recorded on specific forms as follows.  
• 
Any allergic symptoms observed during in-clinic dosing will be recorded directly on 
the Escalation/In-Clinic Dosing Form (also referred to as a Study Product 
Administration Form), and are not recorded on an AE form (to avoid duplicate 
reporting) unless the event is considered an SAE. These symptoms are, however, by 
definition, AEs (Section 7.2) and will be reported as such in the database.  
• 
Non-serious AEIs are reported on an AEI form and include anaphylaxis episodes 
meeting the criteria below, accidental food allergen exposures, GI AEs resulting in 
prolonged disruption of dosing, AEs associated with the use of epinephrine, and 
severe AEs (Section 7.3.3). 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).  
• 
If any safety event meets the definition of an SAE (whether or not related to dosing), 
it will also be recorded on an AE/SAE form.  
• 
Skin prick test reactions are not considered AEs unless the reaction, or a complication 
from the procedure, is considered an SAE, as defined below (Section 7.3.2).  
• 
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 7.3.2).  
– 
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 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. 
• 
All SAEs are reported on the AE/SAE form set in addition to the Skin Prick Test 
form or an Oral Food Challenge form if the event occurred during 1 of these 

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procedures. All other safety events that occur throughout the study are reported on the 
AE/AEI/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 study product will need to be recorded 
(Section 7.5.1).  
It is common for allergic reactions, especially allergic reactions to food allergens, to manifest 
with multiple symptoms. When multiple symptoms are noted during the same episode, it is 
up to the investigator to determine whether 1, or more than 1, AE has occurred. For allergic/ 
hypersensitivity reactions involving multiple symptoms, each individual symptom is to be 
entered on a separate log line on the AE electronic CRF (eCRF). For each symptom, the AE 
eCRF will query “Is this an allergic reaction?” and the site should indicate yes/no 
accordingly.  
7.3 
Definitions of Safety Events 
7.3.1 
Adverse Event (AE) or Medical Event 
An AE is any untoward medical occurrence in humans, whether or not considered drug 
related that 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.  
A suspected adverse reaction is any AE for which there is a reasonable possibility that the 
drug caused the AE. A reasonable possibility implies that there is evidence that the drug 
caused the event. 
An adverse reaction is any AE caused by the drug.  
7.3.2 
Serious Adverse Events (SAE) 
An SAE is an AE that results in any of the following outcomes: 
 Death 
 Life-threatening AE (Life-threatening means that the study subject was, in the opinion of 
the investigator or Sponsor, at immediate risk of death from the reaction as it occurred.) 
 Inpatient hospitalization or prolongation of existing hospitalization 
 Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
 Congenital abnormality or birth defect 

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 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. 
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 
Adverse Events of Interest 
7.3.3.1 
Anaphylaxis Events 
An anaphylaxis event is an AE that meets the definition of anaphylaxis in the 2014 position 
paper by the European Academy of Allergy and Clinical Immunology (EAACI) Food 
Allergy and Anaphylaxis Guidelines Group (Muraro et al, 2014). Accordingly, anaphylaxis is 
defined as a severe, potentially life-threatening systemic hypersensitivity reaction, 
characterized by being rapid in onset with life-threatening airway, breathing, or circulatory 
problems that is usually, though not always, associated with skin and mucosal changes. 
With respect to the inclusion of being “potentially life-threatening” in the definition of 
anaphylaxis and how that relates to the assessment of anaphylaxis as an SAE, reference is 
made to the 2012 US Food and Drug Administration (FDA) Guidance for Industry and 
Investigators, “Safety Reporting Requirements for INDs and BA/BE Studies,” that states, 
“An adverse event or suspected adverse reaction is considered “life-threatening” if, in the 
view of either the investigator or Sponsor, its occurrence places the patient or subject at 
immediate risk of death. It does not include an adverse event or suspected adverse reaction 
that, had it occurred in a more severe form, might have caused death.” Thus, for the reporting 
of anaphylaxis as an SAE, the severity of the reaction is also to be taken into account.  
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). These criteria were again 
affirmed in the recently published “International consensus on (ICON) anaphylaxis” 
(Simons et al, 2014). 
For the purposes of this protocol, symptoms during DBPCFCs are not considered to be 
anaphylaxis events. 
7.3.3.2 
Gastrointestinal Adverse Events Resulting in Prolonged Disruption of Dosing  
Gastrointestinal AEs, typically chronic/recurrent GI AEs, that result in a prolonged 
disruption of dosing will be considered AEIs and will be assessed longitudinally according to 
the procedures described below. For the purpose of delineating these AEIs, prolonged 

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disruption of dosing is defined as withholding study product 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 7.3.3.2); 
• 
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 6.5.3.2); 
• 
Any subject who permanently discontinues dosing who had experienced a GI AE 
(Section 7.3.3.2).  
Subjects who fall into any of these 3 categories will be asked to fill out the PEESS v2.0 
questionnaire (Franciosi et al 2011), with the assistance of a parent or guardian, as 
appropriate, every month for 6 months. It should, however, be noted that the PEESS v2.0 was 
not designed to establish a diagnosis of EoE, and has not been validated for use in patients 
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 ≥ 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 investigational product, the 
subject should be referred to a (pediatric) gastroenterologist. 
If a subject who discontinued dosing with the investigational product 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 study product was withdrawn, the subject should 
be referred to a (pediatric) gastroenterologist. 
As is the case for any AE occurring during the study, so it is for chronic/recurrent GI AEs 
that the investigator may, at any time, and at his or her discretion, request consultation from 
an outside physician or additional testing to assist in the diagnosis or management of the AE. 
If a subject is seen by a gastroenterologist, the investigational site is to procure records of the 
visit, as well as any test results, including those from endoscopy and endoscopic biopsy, if 
performed. These are to be retained with the subject’s source documentation.  

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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 
below (Section 7.3.2), 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 
The severity of symptoms will be determined based on the investigator’s judgment. Severity 
definitions for allergic reactions to investigational product were developed to be consistent 
both with the PRACTALL consensus report and with the CoFAR grading system and are 
provided in Section 6.5.1 and the table in Appendix 4 as a general guide. Severe allergic AEs 
may include: 
• 
Skin – severe generalized urticaria/angioedema/erythema;  
• 
Respiratory – laryngeal edema, throat tightness with hoarseness, wheezing with 
dyspnea, stridor;  
• 
GI – severe abdominal pain/cramping/repetitive vomiting and/or diarrhea; 
• 
Neurological – change in mental status; 
• 
Circulatory – clinically significant hypotension. 
Severity of other AEs will be assigned using other grading systems as discussed in 
Section 7.4.  
If the severe AE was part of an allergic reaction that meets criteria for anaphylaxis, an 
accidental food allergen exposure, an AE featuring a severe symptom, or an SAE, it 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.   
7.3.3.5 
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 

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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 1 of these 
other categories.  
7.4 
Severity Grading 
The investigator is to assign severity grades to AEs. Depending on the type of AE, different 
severity grading systems will be used in this study. 
• 
The severity grading of allergic reactions will be according to the definitions 
developed by the CoFAR group (Appendix 4) 
• 
The severity of anaphylactic reactions will be graded according to the EAACI system 
for grading the severity of anaphylactic reactions (Appendix 3). 
• 
For grading the severity of all other AEs, the National Cancer Institute’s Common 
Terminology Criteria for Adverse Events (NCI-CTCAE) system will be used. The 
purpose of using the NCI-CTCAE system is to provide standard language to describe 
AEs (“toxicities”) and to facilitate tabulation and analysis of the data and for 
assessment of the clinical significance of treatment-related toxicities. The 
NCI-CTCAE provides a term and a grade that closely describes the AE. Each 
participating site will receive copies of the grading scales and event descriptions.  
For AEs not included in the NCI-CTCAE listing, they are also to be graded on a scale from 
1 to 5, according to the 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.  

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7.4.1 
Guidelines for Determining Causality of an Adverse Event 
The investigator will use the following question when assessing causality of an AE to study 
product: Is there a reasonable possibility that the study product caused the event? 
An affirmative answer designates the event as a suspected adverse reaction. 
7.5 
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 Exit or Early Discontinuation Visit, 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 may 
be required. For the specific case of GI-related AEIs, the need for additional follow-up is 
outlined in Section 7.3.3.2. Investigators should also report AEs discovered after cessation of 
dosing and prior to the Early Discontinuation Visit. 
Adverse events may be discovered through any of these methods: 
• 
Observing the subject 
• 
Questioning the subject, which should be done in an objective manner 
• 
Receiving an unsolicited complaint from the subject 
• 
Review of medical records/source documents 
• 
Review of home dosing symptom logs (provided to record symptoms between visits) 
7.5.1 
Recording and Reporting Procedures 
A multi-screen AE eCRF will be used allowing all AEs to be submitted through a single 
reporting mechanism (Figure 7). Serious AEs will require additional information reported on 
additional screens within the EDC system. Source documents, with subject identifiers 
redacted, can be scanned and attached to the AE form as well. The investigator will treat 
subjects experiencing AEs appropriately and observe them at suitable intervals until their 
symptoms resolve or their status stabilizes. 
7.5.2 
Serious Adverse Event Recording and Reporting Procedures 
Serious AEs will be recorded on the AE CRF. All centers are obligated to report SAEs within 
24 hours of their occurrence and/or the site’s knowledge of the event to the Sponsor. The 
following attributes will be assigned:  
• 
Description 
• 
Date of onset and resolution (if known when reported) 

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• 
Severity 
• 
Assessment of relatedness to test article  
• 
Action taken 
The site investigator will apply his/her clinical judgment to determine whether an AE is of 
sufficient severity to require that the subject be removed from treatment. If necessary, an 
investigator will suspend any trial procedures and institute the necessary medical therapy to 
protect a subject from any immediate danger. 
Subsequent review by regulatory health authority(ies), institutional review board (IRB)/ethics 
committee (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. 
A subject may voluntarily withdraw from treatment due to what he/she perceives as an 
intolerable AE, or for any other reason. If voluntary withdrawal is requested, the subject 
should be asked to continue (at least limited) scheduled evaluations, complete a study 
termination form, and be given appropriate care under medical supervision until the 
symptoms of any AE resolve or his or her condition becomes stable.  
Figure 7: Reporting Decisions for Adverse Events 
 
 
Steps to follow in sequence:   
 Site to notify the site’s Principal Investigator of event(s). 
 Complete and transmit an AE Form through the Internet data entry system. Information 
regarding an SAE report must be recorded in the subject’s medical chart. 

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 SAE follow-up reports should include 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, the SAE form must be completed and transmitted along with 
other supporting data (death certificate, medical notes, etc.). 
7.6 
Serious Adverse Event Notification 
7.6.1 
Notifying the Sponsor 
Study investigators will provide the Reporting Center (ProPharma Group, St. Paul, MN) with 
data of all SAEs as defined per the protocol on an ongoing basis. As noted above, the initial 
contact will be within 24 hours of site’s awareness of the event.  
7.6.2 
Expedited SAEs Reporting to Regulatory Health Authorities 
The Sponsor’s Medical Monitor will review each SAE report and will determine whether the 
SAE must be reported to regulatory health authorities on an expedited basis. The final 
decision for disposition regarding expedited reporting to the regulatory health authorities 
rests with the Sponsor’s Medical Monitor.  
The Sponsor will expedite the reporting to all concerned investigator(s), IRBs/ECs, where 
required, and to the national regulatory authorities of any suspected unexpected serious 
adverse reaction (SUSAR) in accordance with ICH E6 5.16.2 and 5.17.1. 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 5.17.2. 
The Reporting Center 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). 
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. 
7.6.3 
Other Events Reportable to the Sponsor 
Investigational sites are instructed to report all episodes of anaphylaxis meeting the criteria in 
Appendix 3 within 24 hours of their awareness of the event to the Reporting Center; others 
can be reported within 7 days. An initial Anaphylaxis Episode form containing the 
information known to the site at this time will be transmitted to the Reporting Center. The 
Reporting Center will then relay to the Sponsor the individual anaphylaxis reports as they are 
obtained. The investigational site will supplement the initial Anaphylaxis Episode report with 

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additional information pertaining to an event as it becomes available and will forward the 
information to the Reporting Center. The Sponsor’s Medical Monitor reviews these events 
upon receipt and will expedite anaphylaxis events to the SMC if the event is associated with 
any of the following: 
• 
An emergency room visit; 
• 
Hospitalization; 
• 
More than 2 doses of epinephrine being given as treatment for the same episode; 
• 
Assessment of the anaphylaxis as severe, as defined in Appendix 3. 
Anaphylaxis events meeting seriousness criteria will be reported as per other SAEs, as 
outlined above in Section 7.5.2, but in general will not be further reported in expedited 
fashion to regulatory health authorities unless meeting the criteria of a SUSAR.  
7.6.4 
Review Board and Ethics Committee 
The investigator will ensure the timely dissemination of all AE information, including 
expedited reports and Sponsor safety reviews, to the IRB in accordance with applicable local 
regulations and guidelines. 
7.7 
Other Safety Assessments and Precautions 
7.7.1 
Physical Examination and Vital Signs 
Physical examinations will be conducted at visits indicated in the Schedules of Events 
(Appendix 1). Height and weight will also be recorded at specified visits. Vital signs will be 
measured, including BP, PR, and body temperature. Except where a full, age appropriate, 
physical examination is specifically indicated, a symptom-directed physical examination may 
be performed. 
7.7.2 
Prior and Concomitant Medications 
Prior and concomitant medications will be documented in the CRF.  
7.7.3 
Pregnancy Testing and Contraception 
7.7.3.1 
Pregnancy Testing 
All female subjects of child-bearing age will undergo a serum pregnancy test at screening 
and then urine pregnancy test at subsequent visits. 
7.7.3.2 
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 

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blood pressure; if this were to occur during pregnancy, it could result in compromised 
placental perfusion and significant risk to the fetus. 
Pregnancy is a time when the mother’s immune system undergoes complex and incompletely 
understood changes that are believed to reduce the risk of a maternal immune reaction 
directed against the fetus. It is also a time when the fetus’s immune system is developing. 
Oral immunotherapy, at its core, entails repeated stimulation of the immune system to affect 
changes in its makeup and function. What effects OIT-induced changes in the immune 
system might have on the course of pregnancy or fetal development are currently unknown. 
Accordingly, female subjects of childbearing potential are required to practice effective birth 
control for the duration of the current study.  
A female is considered of childbearing potential (ie, fertile, after menarche and until 
becoming postmenopausal) unless permanently sterile. Permanent sterilization methods 
include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.  
A postmenopausal state is defined as no menses for at least 12 months without an alternative 
medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in a female not using hormonal contraception 
or hormonal replacement therapy. A single FSH measurement is considered sufficient only in 
a female who had amenorrhea for at least 12 months. 
Investigators must ensure that all female subjects who are post-menarchal are provided with 
age-appropriate counselling and information about contraception, including adequate 
information about the use, effectiveness and side-effects of contraceptive methods. 
Female subjects are to use either:  
• 
A highly effective method of birth control, defined as one that results in a low failure 
rate (ie, less than 1 percent per year) when used consistently and correctly, such as 
implants, injectables, combined oral contraceptives, some intrauterine contraceptive 
devices, sexual abstinence, or a vasectomized partner; or 
• 
Alternatively, if a highly effective method of birth control is not used, an effective, 
double barrier method of contraception (eg, male condom with female condom, 
cervical cap, diaphragm, or contraceptive sponge) may be used. 
7.8 
Stopping Rules 
7.8.1 
Overall Stopping Rules 
Considerations for early termination of a subject are listed in Section 4.3.1. In addition, this 
protocol will institute the following stopping rules. The study will be suspended at any time 
that a treatment-associated death occurs in a subject receiving AR101 active therapy, or that 
the second of 2 subjects is admitted to the hospital, within 6 months of the first, as a direct 
consequence of dosing with AR101. Suspension of the study will entail halting the 
enrollment of subjects and refraining from any dose increases, but will not entail cessation of 
dosing unless so directed by the relevant competent authority and agreed to by the Sponsor. 

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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.  
Aimmune Therapeutics, Inc. additionally reserves the right to discontinue the study at any 
time for any reason. The regulatory health authority(ies) and IRBs/ECs will be notified in the 
event of study discontinuation. 
7.8.2 
Individual Stopping Rules 
Individuals may stop the study at any time by withdrawing their consent if they experience 
subjectively intolerable AEs, dosing symptoms, or for any other reason. Because ARC004 is 
exploring alternative dosing schedules, the approach to individual stopping rules caused by 
dose-related AEs varies by regimen. All subjects discontinuing the study early and 
permanently discontinuing AR101 treatment will return to the CRC for an Early 
Discontinuation Visit no later than 14 days after the last AR101 exposure.  
QD Dosing Regimens  
When on QD dosing regimens (including Up-dosing and Maintenance for Group 1, and QD 
EM for both Groups, as applicable), 7 or more consecutive days of missed daily dosing due 
to non-compliance constitutes an individual stopping rule. During Up-dosing, Group 1 
subjects must halt up-dosing and re-start with a reduced dose if more than 4 days of dosing 
are missed. Missing 3 or more consecutive days on 3 occasions while on daily dosing in any 
period is an individual stopping rule, as is missing 15 or more consecutive days of QD dosing 
for any reason.  
QOD, BIW, QW, or QOW Regimens 
Any subject receiving nondaily dosing (QOD, BIW, QW, or QOW) who has 1 related SAE; 
1 related AE graded severe; 2 related AEs occurring on separate occasions, both graded 
moderate; or 3 consecutive doses judged “not tolerated” will be considered as a treatment 
failure and discontinued from ARC004 for safety reasons. Such subjects may be eligible to 
enroll in ARC008 and receive AR101 daily in the Repeat Up-dosing period. If ARC008 is 
not available, the subjects will begin daily dosing and have visits in the Repeat Up-dosing 
period in ARC004.  Once the subject reaches the target dose of 300 mg daily and maintains 
that dose for 2 weeks, that subject will be able to continue this dose regimen until ARC008 is 
available.  
Occurrence of any of the following will result in the cessation of dosing and the subject being 
discontinued from the study as an escalation failure nonresponder:  
• 
Failure to accomplish up-dosing of study product after 3 attempts 
• 
Failure to identify a tolerated dose of study product after 3 attempts at dose reduction  

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Finally, administration of 3 or more doses of epinephrine for the treatment of any dose-
related allergic reaction in any subject during any period is an individual stopping rule.  
7.8.3 
Cohort Stopping Rules 
ARC004 will consecutively enroll eligible subjects into different cohorts, each of which will 
produce evidence during the trial concerning the feasibility and safety of adjusting EM 
dosing from daily to a less frequent schedule. The information that becomes available as each 
cohort proceeds through the study will be evaluated before determining whether the next 
cohort is to advance to a longer interval between doses. No subject will be exposed to a 
regimen with longer dosing intervals (eg, QOD to BIW, BIW to QW, or QW to QOW) if 
evidence from the previous cohorts suggests that doing so would more likely than not cause 
subjects at the new interval to either experience more frequent or more severe AEs, or lose 
desensitization that they may have gained/maintained, had they remained on more frequent 
dosing. Because they will have had 28 additional weeks of QD maintenance, Cohorts 3B and 
3C will be allowed to proceed to QOD and BIW dosing independent of Cohort 2’s 
experience according to the judgment of the Safety Monitoring Committee (SMC).  
For each cohort, all subjects discontinuing early due to AEs (eg, dropouts) will be considered 
failures. Likewise, subjects who lose protection during their ARC004 Exit DBPCFC, when 
compared either to their ARC003 Exit DBPCFC (Group 2), or their ARC004 
Post-Maintenance DBPCFC (Group 1) will be considered failures (eg, failed completers), as 
follows: 
• 
Subjects tolerating 443 mg at the previous DBPCFC must tolerate ≥ 443 mg at the 
ARC004 Exit DBPCFC, or be considered a failure 
• 
Subjects tolerating 1043 mg at the previous DBPCFC must tolerate ≥ 443 mg at the 
ARC004 Exit DBPCFC, or be considered a failure 
• 
Subjects tolerating 2043 mg (or greater, for Group 1 subjects) at the previous 
DBPCFC must tolerate ≥ 1043 mg at the ARC004 Exit DBPCFC, or be considered a 
treatment failure 
The treatment failure rate in each cohort will be monitored on an ongoing basis by the SMC, 
and calculated according to the following formula:  
Treatment failure rate = [(dropouts) + (failed completers)] / planned size* for the cohort 
Whenever this number is greater than 50%, then this stopping rule is met and further 
prolongation of the dosing interval in any subsequent cohort will cease. As an additional 
safety precaution, if individual stopping rules (eg, due to AEs) are invoked in 10 of the first 
20 subjects to enroll in any cohort, further enrollment in that cohort will cease. Finally, the 
SMC retains the authority to stop further enrollment into a cohort at any time for any reason. 
If any of these conditions transpire, all remaining subjects, including those ongoing subjects 
in the terminated cohort, and future subjects, will be administered AR101 300 mg at the 
longest interval tolerated by a previous cohort.  

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*Assumptions = Up to approximately 500 ARC003 completers (having received active or 
placebo in ARC003 at a 3:1 ratio) are projected for recruitment into ARC004. This assumes a 
loss of 15% of the randomized ARC003 population due to attrition, AEs, etc. Thus, the 
planned sizes for the ARC004 cohorts is as follows, though the actual number may vary due 
to recruitment:  
• 
Cohort 1 = 120, prespecified  
• 
Cohort 2 = 50, prespecified 
• 
Cohort 3 = 175, distributed equally across Cohorts 3A, 3B, 3C 
• 
Group 1 = 130 (25% of ARC003 enrollment, accounting for 5% dropout) 
8 OPTIONAL MECHANISTIC STUDIES 
Subjects from selected centers in ARC004 are eligible to participate in the optional 
collections of saliva and peripheral blood specimens to be collected for future studies 
designed to better understand the biological basis and treatment of food allergy. These 
additional specimens are entirely voluntary, do not affect the subject’s participation in 
ARC004, and require separate informed consent. The additional tubes of peripheral blood are 
to be collected at the same time points as the routine laboratory work in ARC004 and do not 
require additional visits or phlebotomy. The saliva specimens will be collected as part of an 
ongoing collaboration with researchers at Cincinnati Children’s Hospital Medical Center to 
analyze the salivary mRNA transcriptome of participants receiving OIT, as outlined further 
in Appendix 6.  
9 STATISTICAL CONSIDERATIONS 
This protocol outlines the major statistical considerations for the ARC004 study. Full details 
on the statistical methodology to be used in the analysis and data handling for this trial will 
be described in the statistical analysis plan (SAP) to be developed prior to database lock and 
statistical analysis. 
Data will be summarized using descriptive statistics within treatment group and cohort. 
No specific hypothesis testing or comparisons between the treatment groups is planned for 
this study. Details of within group and within cohort comparisons relative to baseline values 
and exploratory comparisons between cohorts will be described in the SAP. 
Descriptive statistics will be presented in the following manner: 
• 
Continuous data (ie, age, body weight, and height) will be summarized descriptively 
by mean, standard deviation, median, and range. 
• 
Categorical data (ie, sex and race) will be presented as enumerations and percentages. 
Data will be summarized by treatment group, cohort, and treatment phase (as defined in 
Section 3.1).  

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Data will be summarized in tables for each treatment group, treatment groups combined, and 
treatment phase (as defined in Section 3.1).  
Data from ARC003 will be combined with ARC004 and will be used to define baseline, as 
appropriate. Additional details about combining data and handling varying exposure times 
will be described in the SAP. Data will be listed for each subject.  
9.1 
Analysis Populations 
The primary population of analysis for all analyses will be the Safety population. The Safety 
population will consist of all subjects who receive study treatment during ARC004.  
A Per Protocol (PP) population, limited to subjects who have no major protocol deviations 
and who undergo Exit DBPCFC, may be defined. Exclusions will be determined by data 
review and documented before database lock. 
Additional analysis populations may be defined in the SAP. 
9.2 
Study Endpoints 
9.2.1 
Primary Endpoint 
The primary endpoint is the frequency of treatment-related AEs, including SAEs, during the 
overall study period (from enrollment to the end of EM). 
9.2.2 
Secondary Endpoints 
• 
Frequency of anaphylaxis 
• 
Frequency of use of epinephrine as a rescue medication 
• 
Frequency of AEs leading to withdrawal of AR101 
• 
Frequency of AEs in each treatment regimen leading to discontinuation of extended 
interval dosing 
• 
Frequency of GI AEIs 
• 
Frequency of accidental food allergen exposure 
• 
In subjects with asthma, change in asthma control using the Asthma Control Test 
questionnaire (see Appendix 2) 
• 
Frequency of all above safety endpoints by treatment period 
• 
The proportion of subjects in each regimen tolerating ≥ 1043 mg cumulative of 
peanut protein during their EM Exit DBPCFC  
• 
The proportion of subjects in each regimen who tolerate ≥ 443 mg cumulative of 
peanut protein during their EM Exit DBPCFC 
• 
The proportion of subjects in each regimen who tolerate 4043 mg cumulative of 
peanut protein during their EM Exit DBPCFC 

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• 
Maximum tolerated dose and change from baseline* at Post-Maintenance** and each 
EM Exit DBPCFC  
• 
Maximum severity of symptoms at each challenge dose at Post-Maintenance** and 
each EM Exit DBPCFC 
• 
Frequency of use of epinephrine as a rescue medication at the Post-Maintenance** 
and each EM Exit DBPCFC 
• 
Change in QoL as assessed by the FAQLQ and the FAIM questionnaire 
• 
Satisfaction with AR101 treatment as assessed by the TSMQ-9 questionnaire and 
additional questions 
• 
Changes in peanut-specific serum IgE and IgG4 levels 
• 
Changes in peanut skin prick test (SPT) wheal diameter 
*Baseline is defined as the Screening DBPCFC from ARC003 for both treatment groups.  
**Post-Maintenance is defined as the ARC003 Exit DBPCFCs for Group 2. 
9.3 
Subject and Demographic Data 
9.3.1 
Baseline Characteristics and Demographics 
Summary descriptive statistics for baseline and demographic data, collected from ARC003 
and/or ARC004 will be provided for all enrolled subjects. Baseline and demographic data 
will include age, race, sex, body weight, and height. 
Statistical presentation for baseline and demographic characteristics may be further 
summarized by treatment group and baseline peanut-specific serum IgE. 
9.3.2 
Use of Medications 
All medications used will be coded using the World Health Organization (WHO) drug 
dictionary. The number and percentage of subjects receiving concomitant medications or 
therapies will be summarized descriptively. 
9.3.3 
Study Disposition 
The number and percent of subjects in each analysis population will be summarized. The 
number of subjects who complete the study, discontinue prematurely, and their reason for 
study discontinuation will be tabulated. Total duration on treatment and total duration on 
study will also be summarized. 
9.3.4 
Adverse Events 
Adverse events will be coded based on the Medical Dictionary for Regulatory Activities 
(MedDRA) terminology. Events will be tabulated by system organ classification and 
preferred term. Selected summaries will also be prepared by severity and relationship to 

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study treatment. An Adjudication Committee will be convened for this study. The committee 
will adjudicate all SAEs and AEIs. Both the investigator and the adjudicated assessments will 
be reported in the clinical study report.  
9.4 
Sample Size and Power Calculations 
The primary objective of this study is to determine the safety, tolerability, and efficacy of 
AR101 CODIT using alternative maintenance dosing intervals. The sample size for this study 
is based on the number of eligible subjects from study ARC003 consenting to rollover into 
the ARC004 open-label protocol. 
ARC003 had a target enrollment of 500 and a 3:1 AR101:placebo randomization ratio, 
providing 89% power to rule out a treatment difference (AR101 minus placebo) of 15% or 
less at the primary endpoint of the proportion of subjects who tolerate ≥ 1043 mg cumulative 
of peanut protein with no more than mild symptoms at the Exit DBPCFC. Assuming accrual 
of 80% of the total ARC003 sample into ARC004, the total of approximately 400 subjects 
treated with AR101 in the clinical program would provide an 80% probability of observing 
≥ 1 AE when the background rate of the AE is 4 per 1,000 subjects.  
There is no prospective power calculation for efficacy in ARC004. 
10 IDENTIFICATION AND ACCESS TO SOURCE DATA 
10.1 Web-Based Data Collection and Management System 
Data collection will occur via a web-based data entry system to allow easy access to 
enrollment 24 hours a day, 7 days a week. Upon enrollment, a form submission schedule is 
generated for each subject that permits direct access to each eCRF for data entry. As data are 
entered, they are validated through range and within-form consistency checks. The 
investigator must ensure that all web-based CRFs are completed in a timely fashion for each 
subject in the study. 
10.2 Certification in the Use of Web-Based Data Entry System 
The clinic and laboratory staff will be trained in the use of the data entry systems. Once 
certified, users are permitted to enter data into the production system. Access is password 
controlled. Certification for use of the web-based data entry system will be completed via 
telephone and/or web-cast training. 
10.3 Data Management 
Information regarding the subject's history, laboratory tests, nutritional intake, 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. 

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10.4 Access to Data 
The investigational sites shall periodically permit authorized representatives of the IND 
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 (21 CFR 312.62) to retain records for a period of 2 years following the date a 
marketing application is approved for the drug for the indication for which it is being 
investigated; 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 FDA is notified, or longer 
if required by local regulations. 
11 QUALITY CONTROL AND QUALITY ASSURANCE 
11.1 Statement of Compliance 
This study will be conducted using good clinical practice (GCP), as delineated in 
21 CFR Parts 50, 54, 56, and 312 and in the ICH “Guidance for Industry: E6 Good Clinical 
Practice Consolidated Guidance,” 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 documents will be reviewed and approved 
by an appropriate IRB/EC and other applicable health authorities. Any amendments to the 
protocol must also be approved by Aimmune Therapeutics, IRB/EC, and other applicable 
health authorities before they are implemented. Any amendments to the consent materials 
must also be approved by Aimmune Therapeutics and IRB/EC before they are implemented. 
11.2 Informed Consent/Assent 
The informed consent form is a means of providing information about the study to a 
prospective subject or subject's parent/guardian and allows for an informed decision about 
participation in the study. Because the study population will comprise a significant 
percentage of children, parents or legal guardians will be asked to read, sign, and date a 
consent form before a child enters the study, takes study product, or undergoes any 
study-specific procedures. When required, both parents will sign the consent form before a 
child can be enrolled in the study. Children will be asked to sign an assent as appropriate. 
Consent materials for subjects or parents/guardians who do not speak or read English will be 
translated into the appropriate language. The informed consent form will be reviewed to 
determine whether a revision is required whenever the protocol is amended. A copy of the 
informed consent form will be given to a prospective subject or parent/guardian for review. 
The investigator (or designee), will review the consent and answer questions, as well as 
emphasize the need to avoid allergen exposure other than to AR101, and the necessity to 
continue exposure to AR101 to maintain desensitization. The prospective subject or subject's 
parent/guardian will be told that being in the study is voluntary and that he or she may 
withdraw, or withdraw his/her child, from the study at any time, for any reason. 

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11.3 Privacy and Confidentiality 
A subject's privacy and confidentiality will be respected. 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 are the property of the Sponsor and will be sent to the 
Sponsor or designee for storage and analysis. Subject data will be anonymized to maintain 
subject confidentiality. All data sets will be archived by the Sponsor or designee and may be 
made available to interested, outside investigators with approval by the Sponsor. 
The Sponsor will review and approve any abstracts or manuscripts prepared from these data 
prior to their submission.  
13 PROTOCOL DEVIATIONS 
The investigators and site staff will conduct the study in accordance with the protocol. 
Any departure from the study design or procedures constitutes a protocol deviation.  
A major protocol deviation is a protocol deviation that may affect subjects’ rights, safety, or 
well-being and/or the completeness, accuracy, and reliability of the study data. 
A non-major protocol deviation is a protocol deviation that does not have a major impact on 
subjects’ rights, safety, or well-being, or the completeness, accuracy, and reliability of the 
study data. 
13.1 Reporting and Managing Protocol Deviations 
The Principal Investigator has the responsibility to identify, document and report protocol 
deviations. When necessary, the Investigator can implement a deviation to the protocol in 
order to eliminate an immediate hazard to a study subject; however, every effort should be 
made to discuss this with the Sponsor’s Medical Monitor before doing so. Protocol 
deviations may also be identified during site monitoring visits or other reviews of study 
conduct. All protocol deviations will be reported in the clinical database. 
The Sponsor’s Medical Monitor (or designee) has the responsibility to review all protocol 
deviations periodically and to classify them as major or non-major. All major protocol 
deviations require additional documentation as directed by the Sponsor. 
Whenever applicable, corrective and preventive actions will be developed by the site and 
approved by the Sponsor, or developed by the Sponsor and communicated to the site(s) and 
implemented promptly.  

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Protocol deviations must be clearly documented, including the reason for them.   If protocol 
deviations lead to the protocol being amended, the amended protocol will be submitted to the 
relevant IRB/IEC and Regulatory Authorities for review, as appropriate. 

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Arias A, Lucendo AJ. Dietary therapies for eosinophilic esophagitis. Expert Rev Clin Immunol. 
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Varshney P, Jones SM, Scurlock AM, et al. A randomized controlled study of peanut oral immunotherapy: 
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Vickery BP, Berglund JP, Burk CM, et al. Early oral immunotherapy in peanut-allergic preschool children is 
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Vickery BP, Scurlock AM, Kulis M, et al. Sustained unresponsiveness to peanut in subjects who have 
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Vierk K, Falci K, Wolyniak C, Klontz KC. Recalls of foods containing undeclared allergens reported to the US 
Food and Drug Administration, fiscal year 1999. J Allergy Clin Immunol. 2002;109(6):1022-1026. 
Wasserman RL, Sugerman RW, Mireku-Akomeah N, et al. Peanut oral immunotherapy (OIT) of food allergy 
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Wechsler JB, Schwartz S, Amsden K, Kagalwalla AF. Elimination diets in the management of eosinophilic 
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Wen T, Stucke EM, Grotjan TM, et al. Molecular diagnosis of eosinophilic esophagitis by gene expression 
profiling. Gastroenterology. 2013;145(6):1289-1299. 
Wolf WA, Jerath MR, Dellon ES. De-novo onset of eosinophilic esophagitis after large volume allergen 
exposures. J Gastrointestin Liver Dis. 2013;22(2):205-208. 
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Appendix 1: Schedules of Events 
Appendix 1-A: 
Schedule of Events for Group 1 and Subjects Switching to Daily Dosing 
Visit 
Screening/ 
Baseline 
Initial 
Escalation 
Up-dosing/ Repeat Up-Dosinga 
Initial 
Maintenancea 
Unscheduledb 
CRC Up-dosing 
Visits (not 80 mg, 
300 mg, or End of 
Up-dosing) 
80 mg 
Visit 
300 mg 
Visit 
End of 
Up-dosing/ 
Maintenance 
Visit 1 
CRC Dosing 
Maintenance 
Visits 2 and 3 
 
 
Up to 10 days 
after Screening/ 
Baselinec 
~every 2 wks for 
22-40 wksd 
~Week 
10 
≤ Week 
40 
2 Weeks after 
Reaching 
300 mg/d 
Weeks 12, 24e 
Investigator 
Discretion 
Informed consent/assent 
X 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
Medical/allergy history  
X 
 
 
 
 
 
 
 
Diet (food allergen) history 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examinationf 
X 
X 
X 
X 
X 
Xg 
X 
X 
Vital signs (BP, PR, temp) 
X 
X 
X 
X 
X 
X 
X 
X 
PEFR/Spirometry (FEV1)h 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testi 
Serum 
 
 
Urine 
 
Urine 
 
Urine 
FAQLQ & FAIM questionnairej 
X 
 
 
 
 
 
 
 
TSQM-9 and Exit questionnairek 
 
 
 
 
 
 
 
 
Blood 
draw 
Peanut-specific IgE, 
IgG4l 
X 
 
 
 
 
X 
Xx 
X 
CBC 
X 
 
 
 
 
X 
Xx 
X 
Optional extra volume 
for exploratory immune 
studies at selected 
centersm 
X 
 
 
 
 
X 
Xx 
X 

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Visit 
Screening/ 
Baseline 
Initial 
Escalation 
Up-dosing/ Repeat Up-Dosinga 
Initial 
Maintenancea 
Unscheduledb 
CRC Up-dosing 
Visits (not 80 mg, 
300 mg, or End of 
Up-dosing) 
80 mg 
Visit 
300 mg 
Visit 
End of 
Up-dosing/ 
Maintenance 
Visit 1 
CRC Dosing 
Maintenance 
Visits 2 and 3 
 
 
Up to 10 days 
after Screening/ 
Baselinec 
~every 2 wks for 
22-40 wksd 
~Week 
10 
≤ Week 
40 
2 Weeks after 
Reaching 
300 mg/d 
Weeks 12, 24e 
Investigator 
Discretion 
Optional saliva collection at 
selected centers 
 
 
 
 
 
 
 
 
No GI symptoms (controls) 
X 
 
Xo 
 
 
X 
 
 
GI symptoms (cases) 
X 
 
Xo 
 
 
 
 
Xo 
Skin prick test 
X 
 
 
 
 
X 
Xx 
X 
Administration of OIT at sitep 
 
X 
X 
X 
X 
X 
Xw 
X 
Dispense / return unused study 
product 
 
X 
X 
X 
X 
X 
X 
X 
DBPCFC (2 parts within 7 days) 
X 
 
 
 
 
 
Xq,r 
 
Monitor AEs/allergic symptomss 
X 
X 
X 
X 
X 
X 
X 
X 
Monitor for compliance 
X 
 
X 
X 
X 
X 
X 
X 
Assessment of asthma (including 
ACT) 
X 
 
 
X 
 
X 
X 
X 
Subject reminder to avoid peanut; 
allergy training  
X 
X 
X 
X 
X 
X 
X 
X 
Telephone follow-upt,u 
 
X 
X 
X 
X 
X 
X 
X 
PEESS v2.0 questionnaire 
 
 
 
 
 
 
 
Xv 
 
Abbreviations: ACT = Asthma Control Test; AEs = adverse events; AEIs = adverse events of interest; BP = blood pressure; CBC = complete blood count; 
CRC = clinical research center; DBPCFC = double-blind, placebo controlled food challenge; FAIM = food allergy independent measure; FAQLQ = food 
allergy related quality of life questionnaire; FEV1 = forced expiratory volume in 1 second; GI = gastrointestinal; Ig = immunoglobulin; OIT = oral 
immunotherapy; PEESS = Pediatric Eosinophilic Esophagitis Symptom Scores; PEFR = peak expiratory flow rate; PR = pulse rate; temp = body temperature; 
TSQM-9 = Treatment Satisfaction Questionnaire for Medication; wks = weeks  
Footnotes: 
a) Subjects who have the option to switch to AR101 daily in ARC008 may start AR101 daily dosing (Repeat Up-dosing from 80, 120, or 160 mg to 300 mg 
daily) and have visits in ARC004 if ARC008 is not yet available at the study site (Section 3). Repeat Up-dosing may be up to a maximum of 26 weeks.  
b) Any of the procedures performed at CRC dosing visits (except Post-Maintenance DBPCFC) may be performed at unscheduled visits. 

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c) Day 1 of the Initial Escalation Period will be scheduled within 10 days after the ARC003 Exit DBPCFC. See Table 1 for dose escalation schedule. 
Subjects will begin home dosing at dose 3 mg/d on Day 3. 
– Day 1: Escalation to ≥ 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 should occur on the next consecutive day following Day 1.  
d) Subjects return to clinic every 2 weeks for up-dosing to a maximum of 300 mg, following the dose escalation schedule in Table 2, unless up-dosing is 
delayed due to allergic reaction. The Up-dosing Period ends after maintaining the 300-mg dose for 2 weeks. 
e) CRC dosing occurs at Weeks 12 and 24 after entering the Maintenance Period, with a Post-maintenance DBPCFC at Week 24 (approximately).  
f) 
Physical examination to include height and weight. At the investigator’s discretion, limited or symptom-directed physical examinations may be 
completed in CRC dosing visits during the Extended Maintenance Period. Full physical examinations are to be conducted at the Screening/Baseline, 
80 mg Up-dosing Visit, End of Up-dosing/Maintenance Visit 1 (2 weeks at 300 mg), and the Exit/Early Discontinuation visits.  
g) End of Up-dosing/Maintenance Visit 1 physical examination will be a complete physical examination and will include height and weight. 
h) PEFR to be performed in all subjects 6 years of age or older, measured at approximately the same time for each assessment visit; 3 attempts of PEFR 
should be performed, and the best attempt selected. For subjects 4 or 5 years of age, PEFR is 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 (FEV1) is to be performed in subjects 6 years of age or older when PEFR shows a clinically relevant reduction or the 
subject shows clinical deterioration (e.g., active wheeze on physical examination.); 3 attempts of FEV1 should be performed, and the best attempt 
selected. In order to assess whether the subject is able to adequately perform spirometry, the spirometry must be attempted, and any attempt must be 
documented.  
i) 
For females of childbearing potential. 
j) 
FAQLQ and FAIM questionnaires to be filled out after ARC003 Exit DBPCFC and after ARC004 Exit DBPCFC. 
k) TSQM-9 and Exit questionnaires to be answered after Exit DBPCFC. 
l) 
Blood for peanut-specific IgE, IgG4 is to be drawn prior to DBPCFC. 
m) Optional blood draw at selected centers according to local institutional guidelines for minimal risk phlebotomy procedures in children. No more than 
50 mL total within 8 weeks may be drawn. 
n) Blood draw to be collected prior to the Exit DBPCFC.  
o) Subjects withdrawing early from ARC004 with GI symptoms who were not already enrolled in the optional saliva sub-study will be allowed to enroll 
upon early termination. 
p) The first 2 twice weekly (BIW), once weekly (QW), and every other week (QOW) doses (as applicable) administered to Group 1 during the Extended 
Maintenance Period will be in clinic. 
q) Post-Maintenance DBPCFC to 2000 mg (4043 cumulative) peanut protein is performed only at the end of the 24 week 300 mg Maintenance Period (not 
at each CRC dosing visit). 
r) 
DBPCFC to 2000 mg (4043 mg cumulative) peanut protein at Exit visit only. 
s) 
AEs will be evaluated from the onset until the event is resolved or medically stable, or until 30 days after the Early Discontinuation Visit, whichever 
comes first. GI AEIs will be monitored according to Section 7.3.3.2.  
t) 
Telephone follow-up will occur 1 day after each escalation visit and Initial Maintenance visit to inquire about allergic symptoms and promote 
compliance. 

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u) Telephone follow-up will occur 6 weeks before and after each scheduled Initial Maintenance visit to inquire about allergic symptoms and promote 
compliance. 
v) Subjects who fall into any of these 3 categories will be asked to fill out the PEESS v2.0 questionnaire (Franciosi et al, 2011), with the assistance of a 
parent or guardian, as appropriate, every month for 6 months: 
– Any subject whose dose is withheld for > 7 days due to GI AEs and resumes dosing at a reduced dose level (Section 7.3.3.2). 
– 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 6.5.3.2). 
– Any subject who permanently discontinues dosing who had experienced GI AEs (Section 7.3.3.2). 
w) Subjects should not administer their AR101 dose on days when DBPCFC is conducted. 
x) For group 1 subjects only.  Perform before the Post-Maintenance DBPCFC at the end of Initial Maintenance.   

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Appendix 1-B: 
Schedule of Events for Group 1 and Subjects Switching to Daily Dosing (Continued) 
Visit 
Ext 
Maint 
Ext Maint 
Visits 2a / 2b 
(Initiation Visit 
Day 1 and 2) 
Ext Maint 
Visits 3a / 3b 
(Initiation Visit 
Day 1 and 2) 
Ext Maint 
Visits 4a / 4b 
(Initiation Visit 
Day 1 and 2) 
Exit / Early 
Discontinuation 
Unscheduleda 
 
 
~8-24 wks at BIW 
+/- 1 wk 
~8-24 wks at QW 
+/- 1 wk 
~8-24 weeks at QOW 
+/- 1 wk 
 
 
Dosing Interval 
QD 
Begin BIW 
Begin QW 
Begin QOW 
 
 
Informed consent/assent 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
 
 
 
 
 
 
 
 
 
Medical/allergy history  
 
 
 
 
 
 
 
 
 
Diet (food allergen) history 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examinationb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs (BP, PR, temp) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PEFR/Spirometry (FEV1)c 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testd 
Urine 
Urine 
 
Urine 
 
Urine 
 
Urine 
Urine 
FAQLQ & FAIM questionnairee 
 
 
 
 
 
 
 
X 
 
TSQM-9 and Exit questionnaire 
 
 
 
 
 
 
 
Xf 
 
Blood 
draw 
Peanut-specific IgE, IgG4g  
 
X 
 
X 
 
X 
 
X 
X 
CBC 
 
X 
 
X 
 
X 
 
X 
X 
Optional extra volume for 
exploratory immune studies at 
selected centersh 
 
Xi 
 
Xi 
 
Xi 
 
Xi 
X 
Optional saliva collection at selected 
centers 
 
 
 
 
 
 
 
 
 
No GI symptoms (controls) 
 
 
 
 
 
 
 
 
 
GI symptoms (cases) 
 
 
 
 
 
 
 
Xj 
 
Skin prick test 
 
X 
 
X 
 
X 
 
X 
X 
Administration of OIT at site 
Xk,l 
X 
X 
X 
X 
X 
X 
 
X 
Dispense / return unused study 
productm 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Visit 
Ext 
Maint 
Ext Maint 
Visits 2a / 2b 
(Initiation Visit 
Day 1 and 2) 
Ext Maint 
Visits 3a / 3b 
(Initiation Visit 
Day 1 and 2) 
Ext Maint 
Visits 4a / 4b 
(Initiation Visit 
Day 1 and 2) 
Exit / Early 
Discontinuation 
Unscheduleda 
 
 
~8-24 wks at BIW 
+/- 1 wk 
~8-24 wks at QW 
+/- 1 wk 
~8-24 weeks at QOW 
+/- 1 wk 
 
 
Dosing Interval 
QD 
Begin BIW 
Begin QW 
Begin QOW 
 
 
DBPCFC (2 parts within 7 days) 
 
 
 
 
 
 
 
Xn,o 
 
Monitor AEs/allergic symptomsp 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Monitor for compliance 
X 
X 
 
X 
 
X 
 
X 
X 
Assessment of asthma (ACT) 
X 
X 
 
X 
 
X 
 
X 
X 
Subject reminder to avoid peanut; 
allergy training  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Telephone follow-upq,r 
X 
X 
X 
X 
X 
X 
X 
 
X 
PEESS v2.0 questionnaire 
 
 
 
 
 
 
 
Xs 
Xs 
 
Abbreviations: ACT = Asthma Control Test; AEs = adverse events; AEIs = adverse events of interest; BIW = biweekly; BP = blood pressure; 
CBC = complete blood count; CRC = clinical research center; DBPCFC = double-blind, placebo-controlled food challenge; EM, Extended Maintenance 
Period; Ext Maint = Extended Maintenance Period; FAIM = food allergy independent measure; FAQLQ = food allergy related quality of life questionnaire; 
FEV1 = forced expiratory volume in 1 second; GI = gastrointestinal; Ig = immunoglobulin; OIT = oral immunotherapy; PEESS = Pediatric Eosinophilic 
Esophagitis Symptom Scores; PEFR= peak expiratory flow rate; PR = pulse rate; QD = once daily; QOD = every other day; QOW = every other week; 
QW = once weekly; temp = body temperature; TSQM-9 = Treatment Satisfaction Questionnaire for Medication; wk = week 
Footnotes: 
a) Any of the procedures performed at CRC dosing visits may be performed at unscheduled visits. 
b) Physical examination to include height and weight. At the investigator’s discretion, symptom-directed physical examinations may be completed in CRC 
dosing visits during the Extended Maintenance Period. Full physical examinations are to be conducted at the Exit/Early Discontinuation (Termination) 
visit.  
c) PEFR to be performed in all subjects 6 years of age or older, measured at approximately the same time for each assessment visit; 3 attempts of PEFR 
should be performed, and the best attempt selected. For subjects 4 or 5 years of age, PEFR is 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 (FEV1) is to be performed in subjects 6 years of age or older when PEFR shows a clinically relevant reduction or the 
subject shows clinical deterioration (e.g., active wheeze on physical examination.); 3 attempts of FEV1 should be performed, and the best attempt selected. 
In order to assess whether the subject is able to adequately perform spirometry, the spirometry must be attempted, and any attempt must be documented. 
d) For females of childbearing potential. 
e) FAQLQ and FAIM questionnaires to be filled out prior to ARC003 Exit DBPCFC and after ARC004 Exit DBPCFC. 
f) 
TSQM-9 and Exit questionnaires to be answered after exit DBPCFC. 

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g) Blood for peanut-specific IgE, IgG4 to be drawn prior to DBPCFC. 
h) Optional blood draw at selected centers according to local institutional guidelines for minimal risk phlebotomy procedures in children. No more than 
50 mL total within 8 weeks may be drawn. 
i) 
Blood draw to be collected prior to the Exit DBPCFC. 
j) 
Subjects withdrawing early from ARC004 with GI symptoms who were not already enrolled in the optional saliva sub-study will be allowed to enroll 
upon early termination.  
k) The first 2 BIW, QW, and QOW doses (as applicable) administered during EM to Group 1 will be in clinic.  
l) 
Day 1 of the Initial Escalation Period will be scheduled within 10 days after the ARC003 Exit DBPCFC. See Table 1 for dose escalation schedule. 
Subjects will begin home dosing at dose 3 mg/d on Day 3. 
– Day 1: Escalation to ≥ 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 should occur on the next consecutive day following Day 1.  
m) Subjects return to clinic every 2 weeks for up-dosing to a maximum of 300 mg, following the dose escalation schedule in Table 2, unless up-dosing is 
delayed due to allergic reaction. 
n) Post-Maintenance DBPCFC to 2000 mg (4043 cumulative) peanut protein is performed only at the end of the CRC 300 mg dosing period (not at each 
CRC dosing visit). 
o) DBPCFC to 2000 mg (4043 mg cumulative) peanut protein at Exit visit only. For subjects who do not tolerate their nondaily dosing regimen and subjects 
who switch to daily dosing after missing their nondaily dose for > 3 days, the exit DBPCFC will be omitted before discontinuation from ARC004 and 
enrollment in ARC008.  
p) AEs will be evaluated from the onset until the event is resolved or medically stable, or until 30 days after the Early Discontinuation Visit, whichever 
comes first. GI AEIs will be monitored according to Section 7.3.3.2. 
q) Telephone follow-up will occur 1 day after each EM visit to inquire about allergic symptoms and promote compliance. 
r) 
Telephone follow-up will occur 7 weeks before and after each scheduled EM follow-up visit to inquire about allergic symptoms and promote compliance. 
s) 
Subjects who fall into any of these 3 categories will be asked to fill out the PEESS v2.0 questionnaire (Franciosi et al, 2011), with the assistance of a 
parent or guardian, as appropriate, every month for 6 months: 
– Any subject whose dose is withheld for >7 days due to GI AEs and resumes dosing at a reduced dose level (Section 7.3.3.2). 
– 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 6.5.3.2). 
– Any subject who permanently discontinues dosing who had experienced GI AEs (Section 7.3.3.2). 

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Appendix 1-C: 
Schedule of Events for Group 2, Cohort 1 
Visit 
Screening/ 
Baseline Visit 
Days 1-3 
Ext Maint 
~Week 14 
(+/- 1 week) 
Exit Visit 
≥ Week 28 
Early 
Discontinuation 
Visit 
Unscheduleda 
Dosing Interval 
QD Dosing 
Informed consent/assent 
X 
 
 
 
 
Inclusion/exclusion criteria  
X 
 
 
 
 
Medical/allergy history  
X 
 
 
 
 
Diet (food allergen) history 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
Physical examinationb 
X 
X 
X 
X 
X 
Vital signs (BP, PR, temp) 
X 
X 
X 
X 
X 
PEFR/Spirometry (FEV1)c 
X 
X 
X 
X 
X 
Pregnancy testd 
Serum 
 
Urine 
Urine 
Urine 
FAQLQ & FAIM questionnairee 
X 
 
X 
X 
 
TSQM-9 and Exit questionnaire 
 
 
Xf 
Xf 
 
Blood 
draw 
Peanut-specific IgE, IgG4g  
X 
 
X 
X 
X 
CBC 
X 
 
X 
X 
X 
Optional extra volume for exploratory immune 
studies at selected centersh 
X 
 
Xi 
Xi 
X 
Optional saliva collection at selected centers 
 
 
 
 
 
No GI symptoms (controls)  
X 
 
 
 
 
GI symptoms (cases) 
X 
 
Xj 
Xj 
 
Skin prick test 
X 
 
X 
X 
X 
Administration of OIT at site 
 
X 
 
 
X 
Dispense / return unused study product 
Xk 
X 
Xk 
X 
X 
DBPCFC (2 parts within 7 days) 
X 
 
X 
 
 
Monitor AEs / allergic symptomsl 
X 
X 
X 
X 
X 
Monitor for compliance 
 
X 
X 
X 
X 
Assessment of asthma (ACT) 
X 
X 
X 
X 
X 
Subject reminder to avoid peanut; allergy training 
X 
X 
X 
X 
X 

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Visit 
Screening/ 
Baseline Visit 
Days 1-3 
Ext Maint 
~Week 14 
(+/- 1 week) 
Exit Visit 
≥ Week 28 
Early 
Discontinuation 
Visit 
Unscheduleda 
Dosing Interval 
QD Dosing 
Telephone Follow-up 
 
Xm 
 
 
 
PEESS v2.0 questionnaire 
 
 
Xn 
Xn 
Xn 
 
Abbreviations: ACT = Asthma Control Test; AEs = adverse events; AEIs = adverse events of interest; BP = blood pressure; CBC = complete blood count; 
CRC = clinical research center; DBPCFC = double-blind, placebo-controlled food challenge; Ext Maint = Extended Maintenance Period; FAIM = food allergy 
independent measure; FAQLQ = food allergy related quality of life questionnaire; FEV1 = forced expiratory volume in 1 second; GI = gastrointestinal; 
Ig = immunoglobulin; OIT = oral immunotherapy; PEESS = Pediatric Eosinophilic Esophagitis Symptom Scores; PEFR= peak expiratory flow rate; 
PR = pulse rate; QD = once daily; temp = body temperature; TSQM-9 = Treatment Satisfaction Questionnaire for Medication 
Footnotes: 
a) Any of the procedures performed at CRC dosing visits may be performed at unscheduled visits.  
b) Physical examination to include height and weight. At the investigator’s discretion, symptom-directed physical examinations may be completed in CRC 
dosing visits during the Extended Maintenance Period. Full physical examinations are to be conducted at the Screening/Baseline and the Exit/Early 
Discontinuation (Termination) visits.  
c) PEFR to be performed in all subjects 6 years of age or older, measured at approximately the same time for each assessment visit; 3 attempts of PEFR 
should be performed, and the best attempt selected. For subjects 4 or 5 years of age, PEFR is 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 (FEV1) is to be performed in subjects 6 years of age or older when PEFR shows a clinically relevant reduction or the 
subject shows clinical deterioration (e.g., active wheeze on physical examination.); 3 attempts of FEV1 should be performed, and the best attempt selected. 
In order to assess whether the subject is able to adequately perform spirometry, the spirometry must be attempted, and any attempt must be documented. 
d) For females of childbearing potential. 
e) FAQLQ and FAIM questionnaires to be filled out prior to ARC003 Exit DBPCFC and after ARC004 Exit DBPCFC. 
f) 
TSQM-9 and Exit questionnaires to be answered after exit DBPCFC. 
g) Blood for peanut-specific IgE, IgG4 to be drawn prior to DBPCFC.  
h) Optional blood draw at selected centers according to local institutional guidelines for minimal risk phlebotomy procedures in children. No more than 
50 mL total within 8 weeks may be drawn. 
i) 
Blood draw to be collected prior to the Exit DBPCFC. 
j) 
Subjects withdrawing early from ARC004 with GI symptoms who were not already enrolled in the optional saliva substudy will be allowed to enroll upon 
early termination.  
k) Until ARC008 is available, an additional AR101 14-week supply may be dispensed at this visit.  
l) 
AEs will be evaluated from the onset until the event is resolved or medically stable, or until 30 days after the Early Discontinuation Visit, whichever 
comes first. Gastrointestinal AEIs will be monitored according to Section 7.3.3.2. 
m) Telephone follow-up will occur 7 weeks before and after this visit (ie, Weeks 7 and 21) to inquire about allergic symptoms and promote compliance. 

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n) Subjects who fall into any of these 3 categories will be asked to fill out the PEESS v2.0 questionnaire (Franciosi et al, 2011), with the assistance of a 
parent or guardian, as appropriate, every month for 6 months: 
– Any subject whose dose is withheld for > 7 days due to GI AEs and resumes dosing at a reduced dose level (Section 7.3.3.2). 
– 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 6.5.3.2). 
– Any subject who permanently discontinues dosing who had experienced GI AEs (Section 7.3.3.2). 
 

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Appendix 1-D: 
Schedule of Events for Group 2, Cohort 2 
Visit 
Screening/ 
Baseline Visit 
Days 1-3 
Initiation 
Visit Day 1 
2-4 Days after 
Last QOD 
Dose 
Initiation 
Visit Day 2 
2-4 Days after 
Initiation 
Visit Day 1 
Ext Maint 
~Week 14 
(+/- 1 week) 
Exit Visit 
~Week 28 
Early 
Discontinuation 
Unscheduled a 
Dosing Interval 
 
Begin BIW 
BIW Dosing 
Informed consent/assent 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria  
X 
 
 
 
 
 
 
Medical/allergy history  
X 
 
 
 
 
 
 
Diet (food allergen) history 
X 
 
 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
Physical examinationb 
X 
X 
X 
X 
X 
X 
X 
Vital signs (BP, PR, temp) 
X 
X 
X 
X 
X 
X 
X 
PEFR/Spirometry (FEV1)c 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testd 
Serum 
 
 
 
Urine 
Urine 
Urine 
FAQLQ & FAIM questionnairee 
X 
 
 
 
X 
X 
 
TSQM-9 and Exit questionnaire 
 
 
 
 
Xf 
Xf 
 
Blood 
draw 
Peanut-specific IgE, IgG4g  
X 
 
 
X 
X 
X 
X 
CBC 
X 
 
 
X 
X 
X 
X 
Optional extra volume for 
exploratory immune 
studies at selected centersh 
X 
 
 
Xi 
Xi 
X 
X 
Optional saliva collection at 
selected centers 
 
 
 
 
 
 
 
No GI symptoms (controls) 
X 
 
 
 
 
 
 
GI symptoms (cases) 
X 
 
 
 
Xj 
Xj 
 
Skin prick test 
X 
X 
 
X 
X 
X 
X 
Administration of OIT at site 
 
Xk 
X 
X 
 
 
X 
Dispense / return unused study 
product 
X 
 
X 
X 
X 
X 
X 
DBPCFC (2 parts within 7 days) 
X 
 
 
 
X 
 
 

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Visit 
Screening/ 
Baseline Visit 
Days 1-3 
Initiation 
Visit Day 1 
2-4 Days after 
Last QOD 
Dose 
Initiation 
Visit Day 2 
2-4 Days after 
Initiation 
Visit Day 1 
Ext Maint 
~Week 14 
(+/- 1 week) 
Exit Visit 
~Week 28 
Early 
Discontinuation 
Unscheduled a 
Dosing Interval 
 
Begin BIW 
BIW Dosing 
Monitor AEs / allergic symptomsl 
X 
X 
X 
X 
X 
X 
X 
Monitor for compliance 
 
 
 
X 
X 
X 
X 
Assessment of asthma (ACT) 
X 
 
 
X 
X 
X 
X 
Subject reminder to avoid peanut; 
allergy training 
X 
X 
X 
X 
X 
X 
X 
Telephone follow-up 
 
X 
X 
Xm 
 
 
 
PEESS v2.0 questionnaire 
 
 
 
 
Xn 
Xn 
Xn 
 
Abbreviations: ACT = Asthma Control Test; AEs = adverse events; AEIs = adverse events of interest; BIW = biweekly; BP = blood pressure; 
CBC = complete blood count; CRC = clinical research center; DBPCFC = double-blind, placebo-controlled food challenge; Ext Maint = Extended 
Maintenance Period; FAIM = food allergy independent measure; FAQLQ = food allergy related quality of life questionnaire; FEV1 = forced expiratory 
volume in 1 second; GI = gastrointestinal; Ig = immunoglobulin; OIT = oral immunotherapy; PEESS = Pediatric Eosinophilic Esophagitis Symptom Scores; 
PEFR = peak expiratory flow rate; PR = pulse rate; QOD = every other day; temp = body temperature; TSQM-9 = Treatment Satisfaction Questionnaire for 
Medication 
Footnotes: 
a) Any of the procedures performed at CRC dosing visits may be performed at unscheduled visits. 
b) Physical examination to include height and weight. At the investigator’s discretion, symptom-directed physical examinations may be completed in CRC 
dosing visits during the Extended Maintenance Period. Full physical examinations are to be conducted at the Screening/Baseline and the Exit/Early 
Discontinuation (Termination) visits.  
c) PEFR to be performed in all subjects 6 years of age or older, measured at approximately the same time for each assessment visit; 3 attempts of PEFR 
should be performed, and the best attempt selected. For subjects 4 or 5 years of age, PEFR is 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 (FEV1) is to be performed in subjects 6 years of age or older when PEFR shows a clinically relevant reduction or the 
subject shows clinical deterioration (e.g., active wheeze on physical examination.); 3 attempts of FEV1 should be performed, and the best attempt selected. 
In order to assess whether the subject is able to adequately perform spirometry, the spirometry must be attempted, and any attempt must be documented. 
d) For females of childbearing potential. 
e) FAQLQ and FAIM questionnaires to be filled out prior to ARC003 Exit DBPCFC and after ARC004 Exit DBPCFC. 
f) 
TSQM-9 and Exit questionnaires to be answered after Exit DBPCFC. 
g) Blood for peanut-specific IgE, IgG4 to be drawn prior to DBPCFC. 
h) Optional blood draw at selected centers according to local institutional guidelines for minimal risk phlebotomy procedures in children. No more than 
50 mL total within 8 weeks may be drawn. 

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i) 
Blood draw to be collected prior to the Exit DBPCFC. 
j) 
Subjects withdrawing early from ARC004 with GI symptoms who were not already enrolled in the optional saliva substudy will be allowed to enroll upon 
early termination.  
k) For Cohort 2, the first 2 BIW doses administered during Ext Maint will be in clinic. Doses should be at least 3 days apart (eg. Monday and Thursday each 
week) 
l) 
AEs will be evaluated from the onset until the event is resolved or medically stable, or until 30 days after the Early Discontinuation Visit, whichever 
comes first. Gastrointestinal AEIs will be monitored according to Section 7.3.3.2. 
m) Telephone follow-up will occur 7 weeks before and after this visit (ie, Weeks 7 and 21) to inquire about allergic symptoms and promote compliance. 
n) Subjects who fall into any of these 3 categories will be asked to fill out the PEESS v2.0 questionnaire (Franciosi et al, 2011), with the assistance of a 
parent or guardian, as appropriate, every month for 6 months: 
– Any subject whose dose is withheld for > 7 days due to GI AEs and resumes dosing at a reduced dose level (Section 7.3.3.2). 
– 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 6.5.3.2). 
– Any subject who permanently discontinues dosing who had experienced GI AEs (Section 7.3.3.2). 

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Appendix 1-E: 
Schedule of Events for Group 2, Cohort 3A 
Visit 
Screening/ 
Baseline 
Days 1-3 
Ext Maint 1 
~Week 14 
+/- 1 wk 
Ext Maint 2 
~Week 28 
+/- 1 wk 
Ext Maint 3 
~Week 42 
+/- 1 wk 
Exit Visit 
~Week 56 
+/- 1 wk 
Early 
Discontinuation 
Visit 
Unscheduleda 
Dosing Interval 
QD Dosing 
Informed consent/assent 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria  
X 
 
 
 
 
 
 
Medical/allergy history  
X 
 
 
 
 
 
 
Diet (food allergen) history 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
Physical examinationb 
X 
X 
X 
X 
X 
X 
X 
Vital signs (BP, PR, temp) 
X 
X 
X 
X 
X 
X 
X 
PEFR/Spirometry (FEV1)c 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testd 
Serum 
 
Urine 
 
Urine 
Urine 
Urine 
FAQLQ & FAIM questionnairee 
X 
 
 
 
X 
X 
 
TSQM-9 and Exit questionnaire 
 
 
 
 
Xf 
Xf 
 
Blood 
draw 
Peanut-specific IgE, IgG4g  
X 
 
X 
 
X 
X 
X 
CBC 
X 
 
X 
 
X 
X 
X 
Optional extra volume for 
exploratory immune studies 
at selected centersh 
X 
 
X 
 
Xi 
Xi 
X 
Optional saliva collection at selected 
centers 
 
 
 
 
 
 
 
No GI symptoms (controls) 
X 
 
 
 
 
 
 
GI symptoms (cases) 
X 
 
 
 
Xj 
Xj 
 
Skin prick test 
X 
 
X 
 
X 
X 
X 
Administration of OIT at site 
 
X 
X 
X 
 
 
X 
Dispense / return unused study 
product 
X 
X 
X 
X 
X 
X 
X 
DBPCFC (2 parts within 7 days) 
X 
 
 
 
X 
 
 
Monitor AEs / allergic symptomsk 
X 
X 
X 
X 
X 
X 
X 

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Visit 
Screening/ 
Baseline 
Days 1-3 
Ext Maint 1 
~Week 14 
+/- 1 wk 
Ext Maint 2 
~Week 28 
+/- 1 wk 
Ext Maint 3 
~Week 42 
+/- 1 wk 
Exit Visit 
~Week 56 
+/- 1 wk 
Early 
Discontinuation 
Visit 
Unscheduleda 
Dosing Interval 
QD Dosing 
Monitor for compliance 
 
X 
X 
X 
X 
X 
X 
Assessment of asthma (including 
ACT) 
X 
X 
X 
X 
X 
X 
X 
Subject reminder to avoid peanut; 
allergy training 
X 
X 
X 
X 
X 
X 
X 
Telephone follow-upl 
 
X 
 
X 
 
 
X 
PEESS v2.0 questionnaire 
 
 
 
 
Xm 
Xm 
Xm 
 
Abbreviations: ACT = Asthma Control Test; AEs = adverse events; AEIs = adverse events of interest; BP = blood pressure; CBC = complete blood count; 
CRC = clinical research center; DBPCFC = double-blind, placebo-controlled food challenge; Ext Maint = Extended Maintenance Period; FAIM = food allergy 
independent measure; FAQLQ = food allergy related quality of life questionnaire; FEV1 = forced expiratory volume in 1 second; GI = gastrointestinal; 
Ig = immunoglobulin; OIT = oral immunotherapy; PEESS = Pediatric Eosinophilic Esophagitis Symptom Scores; PEFR = peak expiratory flow rate; 
PR = pulse rate; QD = once daily; temp = body temperature; TSQM-9 = Treatment Satisfaction Questionnaire for Medication; wk = week.  
Footnotes: 
a) Any of the procedures performed at CRC dosing visits may be performed at unscheduled visits. 
b) Physical examination to include height and weight. At the investigator’s discretion, symptom-directed physical examinations may be completed in CRC 
dosing visits during the Extended Maintenance Period. Full physical examinations are to be conducted at the Screening/Baseline and the Exit/Early 
Discontinuation (Termination) visits.  
c) PEFR to be performed in all subjects 6 years of age or older, measured at approximately the same time for each assessment visit; 3 attempts of PEFR 
should be performed, and the best attempt selected. For subjects 4 or 5 years of age, PEFR is 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 (FEV1) is to be performed in subjects 6 years of age or older when PEFR shows a clinically relevant reduction or the 
subject shows clinical deterioration (e.g., active wheeze on physical examination.); 3 attempts of FEV1 should be performed, and the best attempt selected. 
In order to assess whether the subject is able to adequately perform spirometry, the spirometry must be attempted, and any attempt must be documented. 
d) For females of childbearing potential. 
e) FAQLQ and FAIM questionnaires to be filled out prior to ARC003 Exit DBPCFC and after ARC004 Exit DBPCFC. 
f) 
TSQM-9 and Exit questionnaires to be answered after Exit DBPCFC. 
g) Blood for peanut-specific IgE, IgG4 to be drawn prior to DBPCFC. 
h) Optional blood draw at selected centers according to local institutional guidelines for minimal risk phlebotomy procedures in children. No more than 
50 mL total within 8 weeks may be drawn. 
i) 
Blood draw to be collected prior to the Exit DBPCFC. 
j) 
Subjects withdrawing early from ARC004 with GI symptoms who were not already enrolled in the optional saliva substudy will be allowed to enroll upon 
early termination.  

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k) AEs will be evaluated from the onset until the event is resolved or medically stable, or until 30 days after the Early Discontinuation Visit, whichever 
comes first. Gastrointestinal AEIs will be monitored according to Section 7.3.3.2. 
l) 
Telephone follow-up will occur 7 weeks before and after each in-clinic visit (ie, Weeks 7, 21, 35, 49, 63, 77, as applicable) to inquire about allergic 
symptoms and promote compliance.   
m) Subjects who fall into any of these 3 categories will be asked to fill out the PEESS v2.0 questionnaire (Franciosi et al, 2011), with the assistance of a 
parent or guardian, as appropriate, every month for 6 months: 
– Any subject whose dose is withheld for > 7 days due to GI AEs and resumes dosing at a reduced dose level (Section 7.3.3.2). 
– 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 6.5.3.2). 
– Any subject who permanently discontinues dosing who had experienced GI AEs (Section 7.3.3.2). 
 

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Appendix 1-F: 
Schedule of Events for Group 2, Cohort 3B 
Visit 
Screening/ 
Baseline 
Ext Maint 
Visit 1 
Ext Maint 
Visit 2 
Ext Maint 
Visits 3a / 3b 
(Initiation 
Day 1 and 2) 
Ext Maint 
Visit 4 
Exit 
Early 
Discontinuation 
Unscheduled a 
 
Days 1-3 
~Week 14 
+/- 1 wk 
~ Week 28 
+/- 1 wk 
~Week 32/33 
+/- 1 wk 
~Week 42 
+/- 1 wk 
~Week 56 
+/- 1 wk 
 
 
Dosing Interval 
QD Dosing 
Begin QOD 
Begin BIW 
BIW Dosing 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria  
X 
 
 
 
 
 
 
 
 
Medical/allergy history  
X 
 
 
 
 
 
 
 
 
Diet (food allergen) history 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examinationb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs (BP, PR, temp) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PEFR/Spirometry (FEV1)c 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testd 
Serum 
 
Urine 
 
 
 
Urine 
Urine 
Urine 
FAQLQ & FAIM questionnairee 
X 
 
 
 
 
 
X 
X 
 
TSQM-9 and Exit questionnaire 
 
 
 
 
 
 
Xf 
Xf 
 
Blood 
draw 
Peanut-specific IgE, 
IgG4g  
X 
 
X 
 
 
 
X 
X 
X 
CBC 
X 
 
X 
 
 
 
X 
X 
X 
Optional extra volume 
for exploratory immune 
studies at selected 
centersh 
X 
 
X 
 
 
 
Xi 
Xi 
X 
Optional saliva collection at 
selected centers 
 
 
 
 
 
 
 
 
 
No GI symptoms (controls) 
X 
 
 
 
 
 
 
 
 
GI symptoms (cases) 
X 
 
 
 
 
 
Xj 
Xj 
 
Skin prick test 
X 
 
X 
X 
 
X 
X 
X 
X 
Administration of OIT at sitek 
 
X 
X 
X 
X 
X 
 
 
X 

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Visit 
Screening/ 
Baseline 
Ext Maint 
Visit 1 
Ext Maint 
Visit 2 
Ext Maint 
Visits 3a / 3b 
(Initiation 
Day 1 and 2) 
Ext Maint 
Visit 4 
Exit 
Early 
Discontinuation 
Unscheduled a 
 
Days 1-3 
~Week 14 
+/- 1 wk 
~ Week 28 
+/- 1 wk 
~Week 32/33 
+/- 1 wk 
~Week 42 
+/- 1 wk 
~Week 56 
+/- 1 wk 
 
 
Dosing Interval 
QD Dosing 
Begin QOD 
Begin BIW 
BIW Dosing 
Dispense / return unused study 
product 
X 
X 
X 
X 
X 
X 
X 
X 
X 
DBPCFC (2 parts within 7 days) 
X 
 
 
 
 
 
X 
 
 
Monitor AEs / allergic symptomsl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Monitor for compliance 
 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of asthma (including 
ACT) 
X 
X 
X 
X 
 
X 
X 
X 
X 
Subject reminder to avoid peanut; 
allergy training 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Telephone follow-upm 
 
X 
X 
 
 
X 
 
 
X 
PEESS v2.0 questionnaire 
 
 
 
 
 
 
Xn 
Xn 
Xn 
 
Abbreviations: ACT = Asthma Control Test; AEs = adverse events; AEIs = adverse events of interest; BIW = biweekly; BP = blood pressure; 
CBC = complete blood count; CRC = clinical research center; DBPCFC = double-blind, placebo-controlled food challenge; Ext Maint = Extended 
Maintenance Period; FAIM = food allergy independent measure; FAQLQ = food allergy related quality of life questionnaire; FEV1 = forced expiratory 
volume in 1 second; GI = gastrointestinal; Ig = immunoglobulin; OIT = oral immunotherapy; PEESS = Pediatric Eosinophilic Esophagitis Symptom Scores; 
PEFR = peak expiratory flow rate; PR = pulse rate; QD = once daily; QOD = every other day; temp = body temperature; TSQM-9 = Treatment Satisfaction 
Questionnaire for Medication; wk = week 
Footnotes: 
a) Any of the procedures performed at CRC dosing visits may be performed at unscheduled visits. 
b) Physical examination to include height and weight. At the investigator’s discretion, symptom-directed physical examinations may be completed in CRC 
dosing visits during the Extended Maintenance Period. Full physical examinations are to be conducted at the Screening/Baseline and the Exit/Early 
Discontinuation (Termination) visits. 
c) PEFR to be performed in all subjects 6 years of age or older, measured at approximately the same time for each assessment visit; 3 attempts of PEFR 
should be performed, and the best attempt selected. For subjects 4 or 5 years of age, PEFR is 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 (FEV1) is to be performed in subjects 6 years of age or older when PEFR shows a clinically relevant reduction or the 
subject shows clinical deterioration (e.g., active wheeze on physical examination.); 3 attempts of FEV1 should be performed, and the best attempt selected. 
In order to assess whether the subject is able to adequately perform spirometry, the spirometry must be attempted, and any attempt must be documented. 

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d) For females of childbearing potential. 
e) FAQLQ and FAIM questionnaires to be filled out prior to ARC003 Exit DBPCFC and after ARC004 Exit DBPCFC. 
f) 
TSQM-9 and Exit questionnaires to be answered after Exit DBPCFC. 
g) Blood for peanut-specific IgE, IgG4 to be drawn prior to DBPCFC. 
h) Optional blood draw at selected centers according to local institutional guidelines for minimal risk phlebotomy procedures in children. No more than 
50 mL total within 8 weeks may be drawn. 
i) 
Blood draw to be collected prior to the Exit DBPCFC. 
j) 
Subjects withdrawing early from ARC004 with GI symptoms who were not already enrolled in the optional saliva substudy will be allowed to enroll upon 
early termination.  
k) The first 2 BIW doses administered during Ext Maint to Cohort 3B will be in clinic. BIW doses should be at least 3 days apart (eg. Monday and Thursday 
each week). 
l) 
AEs will be evaluated from the onset until the event is resolved or medically stable, or until 30 days after the Early Discontinuation Visit, whichever 
comes first. Gastrointestinal AEIs will be monitored according to Section 7.3.3.2. 
m) Telephone follow-up will occur 7 weeks before and after each in-clinic visit (ie, Weeks 7, 21, 35, 49, 63, 77, as applicable) to inquire about allergic 
symptoms and promote compliance.   
n) Subjects who fall into any of these 3 categories will be asked to fill out the PEESS v2.0 questionnaire (Franciosi et al, 2011), with the assistance of a 
parent or guardian, as appropriate, every month for 6 months: 
– Any subject whose dose is withheld for > 7 days due to GI AEs and resumes dosing at a reduced dose level (Section 7.3.3.2). 
– 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 6.5.3.2). 
– Any subject who permanently discontinues dosing who had experienced GI AEs (Section 7.3.3.2). 
 

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Appendix 1-G: 
Schedule of Events for Group 2, Cohort 3C 
Visit 
Screening / 
Baseline 
Ext 
Maint 
Visit 1 
Ext 
Maint 
Visit 2 
Ext Maint 
Visits 
3a / 3b 
(Initiation 
Visit Day 1 
and 2) 
Ext 
Maint 
Visit 4 
Ext Maint 
Visits 
5a / 5b 
(Initiation 
Visit Day 1 
and 2) 
Ext Maint 
Visit 6 
Exit 
Visit 
Early 
Disconti-
nuation 
Unsched-
uled a 
 
Days 1-3 
~Week 
14 
+/- 1 wk 
~Week 
28  
+/- 1 wk 
~Week 
32/33  
+/- 1 wk 
~Week 
42  
+/- 1 wk 
~Wk  
56/57  
+/- 1 wk 
~Week  
70 
+/- 1 wk 
~Week  
84  
+/- 1 wk 
 
 
Dosing Interval 
QD Dosing 
Begin 
QOD 
Begin BIW 
BIW 
Dosing 
Begin  
QW 
QW  
Dosing 
 
 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria  
X 
 
 
 
 
 
 
 
 
 
 
 
Medical/allergy history  
X 
 
 
 
 
 
 
 
 
 
 
 
Diet (food allergen) history 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examinationb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs (BP, PR, temp) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PEFR/Spirometry (FEV1)c 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testd 
Serum 
 
Urine 
 
 
 
Urine 
 
 
Urine 
Urine 
Urine 
FAQLQ & FAIM questionnairee 
X 
 
 
 
 
 
 
 
 
X 
X 
 
TSQM-9 and Exit questionnaire 
 
 
 
 
 
 
 
 
 
Xf 
Xf 
 
Blood 
draw 
Peanut-specific IgE, IgG4g  
X 
 
X 
 
 
 
X 
 
 
X 
X 
X 
CBC 
X 
 
X 
 
 
 
X 
 
 
X 
X 
X 
Optional extra volume for 
exploratory immune 
studies at selected centersh 
X 
 
X 
 
 
 
Xi 
 
 
Xi 
Xi 
X 
Optional saliva collection at 
selected centers 
 
 
 
 
 
 
 
 
 
 
 
 
No GI symptoms (controls) 
X 
 
 
 
 
 
 
 
 
 
 
 
GI symptoms (cases) 
X 
 
 
 
 
 
 
 
 
Xj 
Xj 
 

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Visit 
Screening / 
Baseline 
Ext 
Maint 
Visit 1 
Ext 
Maint 
Visit 2 
Ext Maint 
Visits 
3a / 3b 
(Initiation 
Visit Day 1 
and 2) 
Ext 
Maint 
Visit 4 
Ext Maint 
Visits 
5a / 5b 
(Initiation 
Visit Day 1 
and 2) 
Ext Maint 
Visit 6 
Exit 
Visit 
Early 
Disconti-
nuation 
Unsched-
uled a 
 
Days 1-3 
~Week 
14 
+/- 1 wk 
~Week 
28  
+/- 1 wk 
~Week 
32/33  
+/- 1 wk 
~Week 
42  
+/- 1 wk 
~Wk  
56/57  
+/- 1 wk 
~Week  
70 
+/- 1 wk 
~Week  
84  
+/- 1 wk 
 
 
Dosing Interval 
QD Dosing 
Begin 
QOD 
Begin BIW 
BIW 
Dosing 
Begin  
QW 
QW  
Dosing 
 
 
Skin prick test 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
Administration of OIT at sitek 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
Dispense / return unused study 
product 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
DBPCFC (2 parts within 7 days) 
X 
 
 
 
 
 
 
 
 
X 
 
 
Monitor AEs / allergic symptomsl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Monitor for compliance 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of asthma (including 
ACT) 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
Reminder to avoid peanut; allergy 
training 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Telephone follow-upm 
 
X 
X 
 
 
X 
X 
 
X 
 
 
X 
PEESS v2.0 questionnaire 
 
 
 
 
 
 
 
 
 
Xn 
Xn 
Xn 
 
Abbreviations: ACT = Asthma Control Test; AEs = adverse events; AEIs = adverse events of interest; BIW = biweekly; BP = blood pressure; 
CBC = complete blood count; CRC = clinical research center; DBPCFC = double-blind, placebo-controlled food challenge; Ext Maint = Extended 
Maintenance Period; FAIM = food allergy independent measure; FAQLQ = food allergy related quality of life questionnaire; FEV1 = forced expiratory 
volume in 1 second; GI = gastrointestinal; Ig = immunoglobulin; OIT = oral immunotherapy; PEESS = Pediatric Eosinophilic Esophagitis Symptom Scores; 
PEFR = peak expiratory flow rate; PR = pulse rate; QD = once daily; QOD = every other day; QW = once weekly; temp = body temperature; 
TSQM-9 = Treatment Satisfaction Questionnaire for Medication; wk = week 
Footnotes: 
a) Any of the procedures performed at CRC dosing visits may be performed at unscheduled visits. 
b) Physical examination to include height and weight. At the investigator’s discretion, symptom-directed physical examinations may be completed in CRC 
dosing visits during the Extended Maintenance Period. Full physical examinations are to be conducted at the Screening/Baseline and the Exit/Early 
Discontinuation (Termination) visits.  

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c) PEFR to be performed in all subjects 6 years of age or older, measured at approximately the same time for each assessment visit; 3 attempts of PEFR 
should be performed, and the best attempt selected. For subjects 4 or 5 years of age, PEFR is 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 (FEV1) is to be performed in subjects 6 years of age or older when PEFR shows a clinically relevant reduction or the 
subject shows clinical deterioration (e.g., active wheeze on physical examination.); 3 attempts of FEV1 should be performed, and the best attempt selected. 
In order to assess whether the subject is able to adequately perform spirometry, the spirometry must be attempted, and any attempt must be documented. 
d) For females of childbearing potential. 
e) FAQLQ and FAIM questionnaires to be filled out prior to ARC003 Exit DBPCFC and after ARC004 Exit DBPCFC. 
f) 
TSQM-9 and Exit questionnaires to be answered after Exit DBPCFC. 
g) Blood for peanut-specific IgE, IgG4 to be drawn prior to DBPCFC.  
h) Optional blood draw at selected centers according to local institutional guidelines for minimal risk phlebotomy procedures in children. No more than 
50 mL total within 8 weeks may be drawn. 
i) 
Blood draw to be collected prior to the Exit DBPCFC. 
j) 
Subjects withdrawing early from ARC004 with GI symptoms who were not already enrolled in the optional saliva substudy will be allowed to enroll upon 
early termination.  
k) The first 2 BIW and QW doses administered during Ext Maint to Cohort 3C will be in clinic. BIW doses should be at least 3 days apart (eg. Monday and 
Thursday each week). QW doses should be taken on the same day (± 1 day) each week. 
l) 
AEs will be evaluated from the onset until the event is resolved or medically stable, or until 30 days after the Early Discontinuation Visit, whichever 
comes first. Gastrointestinal AEIs will be monitored according to Section 7.3.3.2. 
m) Telephone follow-up will occur 7 weeks before and after each in-clinic visit (ie, Weeks 7, 21, 35, 49, 55, 63, 77, as applicable) to inquire about allergic 
symptoms and promote compliance.   
n) Subjects who fall into any of these 3 categories will be asked to fill out the PEESS v2.0 questionnaire (Franciosi et al, 2011), with the assistance of a 
parent or guardian, as appropriate, every month for 6 months: 
– Any subject whose dose is withheld for > 7 days due to GI AEs and resumes dosing at a reduced dose level (Section 7.3.3.2). 
– 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 6.5.3.2). 
– Any subject who permanently discontinues dosing who had experienced GI AEs (Section 7.3.3.2). 
 

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Appendix 2: Evaluation of Asthma 
The evaluation of asthma severity will be assessed using the National Heart, Lung, and Blood 
Institute (NHLBI) classification published 28 August 2007 as described in the table below. 
Table: 
National Heart, Lung, and Blood Institute (NHLBI) Classification 
Classification 
Symptoms 
Nighttime 
awakenings 
Lung Function 
Interference 
with normal 
activity 
Short acting 
beta-agonist 
use 
Intermittent 
(Step 1) 
≤ 2 days per 
week 
≤ 2× /month 
Normal FEV1 
between 
exacerbations 
FEV1 > 80% 
predicted 
FEV1/FVC normal* 
None 
≤ 2 days 
/week 
Mild Persistent 
(Step 2) 
> 2 days per 
week but 
not daily 
3-4× /month 
FEV1 ≥ 80% 
predicted 
FEV1/FVC normal* 
Minor 
limitation 
> 2 days 
/week but not 
>1×/day 
Moderate 
Persistent 
(Step 3 or 4) 
Daily 
> 1× /week 
but not 
nightly 
FEV1 ≥ 60% but 
< 80% predicted 
FEV1/FVC reduced 
5%* 
Some 
limitation 
Daily 
Severe 
Persistent 
(Step 5 or 6) 
Throughout 
the day 
Often  
7× /week 
FEV1 < 60% 
predicted 
FEV1/FVC reduced 
> 5%* 
Extremely 
limited 
Several times 
per day 
*Normal FEV1/FVC: 8 to 19 years of age = 85%; 20 to 39 years of age = 80%.   
FEV1 = forced expiratory volume in the first second of expiration; FVC = forced vital capacity.   
 

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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 is fulfilled: 
 Acute onset of an illness (minutes to hours) with involvement of: 
• 
Skin/mucosal tissue (eg, generalized hives, itch or flush, swollen lips/tongue/uvula) 
AND 
• 
Airway compromise (eg, dyspnea, stridor, wheeze/ bronchospasm, hypoxia, reduced 
peak expiratory flow rate [PEFR]) AND/OR 
• 
Reduced blood pressure (BP) or associated symptoms (eg, hypotonia, syncope, 
incontinence) 
 Two or more of the following that occur rapidly after exposure to the allergen (minutes to 
hour): 
• 
Skin/mucosal tissue (eg, generalized hives, itch/flush, swollen lips/tongue/uvula) 
• 
Airway compromise (eg, dyspnea, stridor wheeze/bronchospasm, hypoxia, reduced 
PEFR) 
• 
Reduced BP or associated symptoms (eg, hypotonia, syncope, incontinence) 
• 
Persistent gastrointestinal (GI) symptoms (eg, nausea, vomiting, crampy abdominal 
pain) 
 Reduced BP after exposure to the allergen (min to h): 
• 
Infants and Children: low systolic BP (age-specific) or > 30% drop in systolic BP* 
• 
Adults: systolic BP < 90 mmHg or > 30% drop from baseline 
* Low systolic BP for children is defined as < 70 mm Hg from 1 month to 1 year; less 
than (70 mm Hg + [2 × age]) from 1 to 10 years; and < 90 mm Hg from age 11 to 
17 years. 
Note: Isolated skin or mucosal lesions following the ingestion of a food constitute a “food-
induced allergic reaction”. 
Table: 
Criteria for Severity Grading 
Staging System of Severity of Anaphylaxis 
Stage 
Defined By 
1. Mild (skin & subcutaneous tissues, 
GI, &/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 & retractions; crampy abdominal pain, 
recurrent vomiting and/or diarrhea; and/or mild dizziness 
3. Severe (hypoxia, hypotension, or 
neurological compromise) 
Cyanosis or SpO2 ≤ 92% at any stage, hypotension, 
confusion, collapse, loss of consciousness; or incontinence 
Criteria for diagnosis and for severity grading have been adapted from Muraro et al, 2007, and Muraro et 
al, 2014.  
 

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Appendix 4: Allergic Reaction Severity Grading 
The Consortium of Food Allergy Research (CoFAR) grading system for allergic reactions is 
displayed in the table below.  
Table: 
CoFAR Specific Grading System for Allergic Reactions 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Life Threatening 
Grade 5 
Death 
Transient or 
mild discomforts 
(< 48 hours), no 
or minimal 
medical 
intervention/ 
therapy required. 
These symptoms 
may include 
pruritus, 
swelling or rash, 
abdominal 
discomfort or 
other transient 
symptoms. 
Symptoms that 
produce mild to 
moderate limitation 
in activity some 
assistance may be 
needed; no or 
minimal 
intervention/therapy 
is required. 
Hospitalization is 
possible. These 
symptoms may 
include persistent 
hives, wheezing 
without dyspnea, 
abdominal 
discomfort/increased 
vomiting or other 
symptoms 
Marked limitation 
in activity, some 
assistance usually 
required; medical 
intervention/therapy 
required. 
Hospitalization is 
possible. Symptoms 
may include 
bronchospasm with 
dyspnea, severe 
abdominal pain, 
throat tightness with 
hoarseness, 
transient 
hypotension among 
others. Parenteral 
medication(s) are 
usually indicated. 
Extreme limitation in 
activity, significant 
assistance required; 
significant 
medical/therapy. 
Intervention is required; 
hospitalization 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 
For an episode of anaphylaxis to be considered a serious adverse event (SAE), Aimmune 
Therapeutics advises that the event satisfy one of the outcome-based definitions of SAE 
specified in Section 7.3.2.  
In this protocol, with the stipulations (denoted in italics) indicated, these stipulations follow 
from, and are consistent with, the criteria for safety monitoring committee (SMC) reporting 
(Section 7.5.2): 
 Death – No further stipulation. 
 Life-threatening adverse event (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 Appendix 4. 
 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. 
 Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions: No further stipulation. 
 Congenital abnormality or birth defect: No further stipulation. 
 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 one of the outcomes listed in the above definition of serious event: 
• 
In general, for an anaphylactic episode to be classified as an SAE based on being an 
“important medical event,” it should have resulted in an emergency room visit, and 
the emergency room 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 intravenous epinephrine, intubation, or admission to an 
intensive care unit. 
• 
One or 2 intramuscular injections of epinephrine should ordinarily not be construed 
as intensive therapy 
• 
If an investigator assesses an episode of anaphylaxis to be an “important medical 
event” when the episode was of mild or moderate severity and did not require 
intensive therapy, the rationale for the assessment must be explained in detail in the 
narrative of the event. 

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Appendix 6: Exploratory Biochemical and Molecular Substudy of Peanut-Allergic 
Children and Adults with Oral Immunotherapy-related Gastrointestinal 
Symptoms in Study ARC004 
Background 
A strong association exists between food allergy and eosinophilic esophagitis (EoE) (Noel et 
al, 2004; Spergel et al, 2012; Greenhawt and Aceves, 2014). Instituting an elemental diet free 
of potential allergens is the most reliably effective treatment for spontaneously occurring 
EoE (Arias and Lucendo, 2014; Wechsler et al, 2014). In some cases of EoE, if a specific 
allergy-provoking food can be identified, then dietary avoidance of the offending food can 
result in resolution of the esophageal symptoms (Spergel et al, 2012). Alternatively, 
elimination from the diet of the most common food allergens, including milk, egg, 
peanut/tree nuts, soy, wheat, and shellfish/fish, can also result in resolution of the esophagitis 
(Kagalwalla et al, 2006; Gonsalves, 2012). When reintroduction of a suspected allergenic 
food is associated with the return of symptoms, this strongly implicates the food as a likely 
causative agent of the EoE (Gonsalves, 2012).  
IgE-mediated hypersensitivity to food allergens, but also aeroallergens (Alpan et al, 2012; 
Ridolo et al, 2012; Wolf et al, 2013; Rea et al, 2014), figures prominently in the pathogenesis 
of EoE, but other factors besides the induction of an immediate hypersensitivity reaction also 
appear important. One circumstance in which multiple factors pertaining to food exposure 
are controlled at the time that EoE becomes symptomatic is when EoE occurs in the setting 
of oral immunotherapy (OIT). The inciting food is known, as is the amount and timing of its 
consumption. Moreover, EoE occurs only in a minority of patients undergoing OIT. Thus, 
studying EoE when it arises during the course of OIT may provide a unique opportunity to 
gain insights into its pathogenesis.  
In OIT studies, gastrointestinal adverse events (GI AEs) are typically prominent (Anagnostou 
et al, 2014; Yu et al, 2012; Blumchen et al, 2010; Jones et al, 2009) and account for a 
substantial proportion of premature discontinuations of study treatment (Burks et al, 2012; 
Varshney et al, 2011; Jones et al, 2009; Vickery et al, 2011). This was also observed in the 
completed ARC001 study and the ongoing ARC002 study. In the ARC001 study, 6 out of 29 
subjects (21%) receiving active treatment discontinued prematurely. Four of the early 
discontinuations were attributed by the Principal Investigators to have been the consequence 
of recurrent GI AEs; in 1 of these cases the diagnosis of EoE was subsequently established 
by endoscopic biopsy. In the other 3 discontinuations, ≥ 1 GI AE had occurred in each 
subject. In the ongoing ARC002 study, an open-label follow-on to the ARC001 study, 6 of 
the 26 subjects (22%) who had been assigned to the placebo group in ARC001 discontinued 
therapy prematurely. Four of these early discontinuations were due to recurrent GI AEs and 2 
were due to study visit scheduling difficulties.  
Repeated bouts of abdominal pain and vomiting are common to both EoE and 
chronic/recurrent OIT-related GI symptoms, suggesting a common, or at least a similar, 
etiology in at least a proportion of patients. To date, ≥ 20 occurrences of OIT-related GI AEs 
have been confirmed histopathologically to be EoE as reported in the medical literature 
(Hofmann et al, 2009; Vickery et al, 2011; Wasserman et al, 2011; Sánchez-García et al, 

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2012; Lucendo et al, 2014), and in still other cases the symptomatology and clinical course 
(with or without concomitant blood eosinophilia) have been highly suggestive of EoE 
(Narisety et al, 2009; Vickery et al, 2011). A recent review of the literature (Lucendo et al, 
2014) has indicated that the incidence of confirmed EoE in OIT is on the order of 3% 
(ranging from approximately 1% to 5%), but the incidence of suspected EoE on clinical 
grounds may be in the vicinity of 15 to 25%. 
Establishing the association between OIT and the subsequent development of EoE is not 
always straight forward. The time to onset of EoE during the course of OIT may vary 
depending on the allergen and OIT regimen. Many (Vickery et al, 2011; Wasserman et al, 
2011), though not all (Hofmann et al, 2009), of the reported cases of EoE with peanut OIT 
had developed GI symptoms early in the course of oral desensitization, whereas with milk 
OIT the occurrence of EoE has tended to be after reintroduction of milk into the diet 
(Sánchez-García et al, 2012; Maggadottir et al, 2014). Not all EoE occurring during OIT is 
necessarily caused by the OIT, however. Food allergies often occur to more than 1 type of 
food and allergies to foods often coexist with allergies to airborne and contact allergens.  
Chronic GI AEs affecting participants in ARC003 and ARC004 have been designated as 
adverse events of interest (AEIs) in the ARC003 and ARC004 protocols. The goal of the 
current substudy is to explore the biology of these GI AEIs occurring during exposure to 
study product using a readily available and noninvasive sampling method (saliva) in an 
attempt to overcome some of the difficulties in assessing intolerable GI AEs in subjects 
undergoing OIT.  
Rationale for the Proposed Study 
The overall aims of this substudy are to collect biospecimens through a noninvasive 
technique, and to analyze them to develop a better understanding of the biochemical and 
molecular changes that occur when OIT participants develop GI AEs significant enough to 
require discontinuation of the OIT protocol. We will obtain preliminary information 
regarding these biological changes in biospecimens from symptomatic individuals, as well as 
controls, using methods that have been developed for the study of eosinophilic GI disorders 
at Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA.  
Specifically, this substudy of ARC004 will enroll all willing volunteers at screening and then 
collect further information from those subjects who go on to experience GI side effects 
during OIT, and controls. To overcome the obstacles limiting traditional EoE evaluations in 
this context (eg, performance of an esophagogastroduodenoscopy [EGD]), an easily collected 
biospecimen will be analyzed to determine whether patterns can be detected that correlate 
with patterns seen in other subjects with known bona fide EoE. As there are no known 
clinical predictors of EoE, all ARC004 participants will be approached about participating in 
this substudy, including those who may have participated in it during ARC003. Further 
analyses will be conducted on those subjects who develop GI symptoms during the course of 
OIT and controls who do not develop GI symptoms. While all subjects who consent to 
participate will provide baseline saliva specimens (collected at screening), we will be 
opportunistic about the collection of esophageal specimens, which may provide additional 
supportive data. Specifically, if subjects in the study withdraw from OIT and undergo a 

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clinically-indicated EGD, we will, whenever possible, collect biopsy material from the site 
for further analysis, as per the ARC004 protocol.  
In addition to addressing the detection of biomolecular signatures in subjects having AEs, it 
is possible that specific biomolecular signatures could emerge from the planned study that 
associate with treatment success or treatment withdrawal. Thus, a possibility exists that the 
proposed biospecimen testing could yield biomarkers predictive of an individual subject’s 
response to OIT and the collection of biospecimens in this substudy could facilitate these 
future analyses. 
Known and Potential Risks and Benefits to Human Participants 
Risks  
The principal potential risk associated with this substudy is the potential for emotional or 
psychological distress related to the discovery of uncertain information that is not itself 
diagnostic but may suggest a new clinical diagnosis (ie, EoE). To mitigate against this risk, 
and because the assays run in this substudy are experimental, exploratory, and not part of 
standard care EoE diagnostics, the results of these studies will not be shared with 
participants. Clinical management of these individuals will be at the judgment of the site 
investigator, per the current standard of care. The ARC004 protocol also contains specific 
recommendations about the clinical follow-up of subjects developing AEIs. All study 
candidates entering ARC004 will undergo an informed consent procedure detailing the 
potential risk of OIT-associated GI symptoms, including the possibility of EoE.  
There are no known physical risks to the saliva collection procedure.  
Benefits  
Individual subjects are not expected to benefit from participation in this study. Information 
from this study may help researchers to better understand peanut allergy and its relationship 
to EoE or to develop future tests or treatments to help patients with 1 or both conditions. 
Objectives 
Primary Objective 
The primary objective is to analyze biomolecular expression patterns in saliva samples 
obtained longitudinally from peanut-allergic participants undergoing OIT in ARC004. These 
studies will target the salivary RNA transcriptome, and if necessary further validate, with 
molecular-, cellular-, and/or protein-based approaches, the expression profile of gene 
pathways that are likely relevant to intolerable GI side effects in ARC004 subjects. 
Secondary Objectives 
The key secondary objective is to examine the relationship of the RNA expression profile to 
selected clinical variables from ARC004, including: 

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• 
The frequency and severity of AEs related to the GI tract 
• 
The frequency of dosing interruptions (reductions and/or discontinuations) directly 
related to GI AEs 
• 
Peripheral blood eosinophil counts 
• 
Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS) v2.0 scores  
• 
Immunoglobulin levels (IgE, IgG4, and their subclasses) 
Further secondary objectives include the correlation of salivary RNA transcriptome data to 
histopathologic and molecular analyses of the esophagus, when available. 
Substudy Design 
This is an optional substudy in which samples will be obtained from ARC004 participants 
according to the Schedule of Events for the substudy in the table below. Only subjects 
enrolled at selected centers in ARC004 and providing additional consent for this substudy are 
eligible to participate. Subjects in either Group 1 or Group 2 who enrolled in this substudy in 
ARC003 will be encouraged to continue participation in ARC004 but will need to be re-
consented to do so. Subjects enrolled in both ARC004 and this substudy will undergo saliva 
collection coordinated at the designated ARC004 study visits. Otherwise these subjects will 
be treated according to the ARC004 study protocol. 
Schedule of Events for the Exploratory Biochemical and Molecular Substudy 
 
Screening 
Early 
Build-up 
Visit 
At PEESS 
v2.0 #1 
End of 
Up-dosing 
Visit 
Post-OIT 
Follow-upb 
Study Weeka 
0 
6 (±2 wk) 
Varies 
20 
Varies  
Informed consent/assent 
X 
 
Xc 
 
 
Saliva collection and 
packaging/shipping: 
 
 
 
 
 
No GI symptoms (controls) 
X 
X 
 
X 
 
GI symptoms (cases) 
X 
 
Xc 
 
X 
Abbreviations: GI = gastrointestinal; OIT = oral immunotherapy; wk = weeks 
a 
Minimum study weeks are shown. Actual duration may be longer depending on subject’s actual 
up-dosing in ARC004.  
b 
For subjects who terminate dosing and enter observational follow-up, as per Section 7.3.3.2 of the 
ARC004 protocol. This sample is to be collected at the sixth monthly visit after study withdrawal or 
as close as practicable.  
c 
Subjects withdrawing early from ARC004 with GI symptoms that were not already enrolled in this 
substudy may be approached to provide consent to enroll upon early termination. 
 
Group 2 subjects (ie, subjects receiving active treatment with AR101 in ARC003) who were 
previously consented for this substudy in ARC003 and elect to continue in ARC004 will not 
provide additional specimens unless they develop symptoms during ARC004. Group 1 

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subjects in this substudy will undergo 3 protocol-specified collections of saliva. All Group 1 
subjects will have a baseline saliva sample collected at Screening and baseline (before the 
first dose of AR101 in ARC004). Subjects who develop GI-predominant AEs that prompt 
their withdrawal from ARC004 or a protracted disruption of dosing with study product will 
be considered “cases” in this substudy. The second saliva sample will be collected from cases 
when the first PEESS v2.0 is completed. The final saliva sample for cases will be collected at 
the end of the protocol-defined 6-month follow-up period for subjects that withdraw from 
therapy. 
“Controls” in this substudy will be defined as ARC004 participants receiving OIT who do 
not develop intolerable GI symptoms. Following the baseline collection, asymptomatic 
subjects will provide saliva samples at the 6-week up-dosing visit and again at the end of the 
Up-dosing period.  
This substudy will principally involve: collection, shipment, and banking of saliva samples at 
specified time points; gene expression analysis of selected salivary biospecimens; and 
correlation with basic biometric data (eg, peripheral blood eosinophils, clinical symptom 
reports/PEESS v2.0 scores) obtained as necessary, and clinical outcome per the ARC004 
protocol. Biochemical detection of eosinophil activation products or metabolites may also be 
possible from collected samples. 
Subject participation will consist of signing an informed consent form approved by the 
institutional review board (IRB), ethics committee, research ethics board, or like authority, 
and age-appropriate assent form, when indicated, as per local guidelines, and the provisions 
for biospecimen collection and handling. 
Case Definition: ARC004 Events Triggering PEESS v2.0  
The following passage is adapted from Section 7.3.3.2 of the ARC004 Protocol, and serves to 
identify the case definition in this substudy; eg, the ARC004 subjects who develop the GI 
AEIs requiring further evaluation.  
GI AEs, typically chronic/recurrent GI AEs, that result in a prolonged disruption of 
dosing will be considered AEIs and will be assessed longitudinally according to the 
procedures described below. For the purpose of delineating these AEIs, prolonged 
disruption of dosing is defined as withholding study product 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 7.3.3.2 of the ARC004 protocol) 
• 
Any subject who develops chronic/recurrent GI AEs at or before reaching the 20-mg 
dose level and resumes dosing after a 30-day dosing hiatus (Section 7.3.3.2 of the 
ARC004 protocol); 
• 
Any subject who permanently discontinues dosing who had experienced GI AEs 
(Section 7.3.3.2 of the ARC004 protocol). 

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Subjects under the age of 18 who fall into any of these 3 categories will be asked to fill 
out the PEESS v2.0 questionnaire (Franciosi et al, 2011), with the assistance of a parent 
or guardian, as appropriate, every month for 6 months; adults will be given the same 
version of the questionnaire. It should, however, be noted that the PEESS v2.0 was not 
designed to establish a diagnosis of EoE, and has not been validated for use in patients 
with GI symptoms of other etiologies. Furthermore, the discriminant validity of the 
questionnaire has not been reported in either longitudinal natural history or 
interventional studies. For these reasons, the use of the PEESS v2.0 to monitor the 
clinical course of GI symptoms must be considered exploratory. Nevertheless, the 
PEESS v2.0 has shown good content and construct validity (Franciosi et al 2011; 
Martin et al 2015) and so holds promise for being a valuable tool to follow the clinical 
course of EoE or an EoE-like immune-mediated GI syndrome. Thus, the PEESS v2.0, 
could reveal trends toward symptomatic improvement or worsening that might otherwise 
go undetected. 
Exploratory Endpoints 
All endpoints in this substudy are considered exploratory. The primary objective is to 
characterize RNA expression patterns in salivary specimens collected from peanut-allergic 
subjects who participated in a study of peanut OIT and developed intolerable GI AEs that 
interfered with treatment (ie, resulted in reducing, withholding, or discontinuing OIT dose 
levels). ARC004 subjects who do not develop dose-limiting GI symptoms will also be 
studied as control specimens. Secondarily we will also examine the associations of the 
salivary RNA expression changes with selected clinical variables and explore the within-
subject correlation to RNA expression patterns observed in esophageal specimens, when 
available.  
Bioinformatic Analysis Plan for Primary and Secondary Objectives  
The bioinformatic analysis plan for the primary and secondary objectives of this study 
include: 
• 
Quality control of the genome-wide RNA sequencing data 
• 
Expression filter and statistical filter 
• 
Clustering analysis with known clinical outcomes 
• 
Develop an algorithm (similar to Wen et al, 2013) to quantify the oral sample 
signature to correlate with the PEESS v2.0 
• 
Use a portion of the samples as a training set for machine learning, then carry out the 
support vector machines (SVMs) to predict the rest of the samples. The SVM is a 
supervised learning model with associated learning algorithms that analyze data and 
recognize patterns.  
• 
Principal Component Analysis (PCA) will be employed to globally categorize the 
samples, reduce the dimensionality for signature quantification, and aid the graphical 
presentation of the data 

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Additional exploratory endpoints may include qualitative and/or quantitative comparisons to 
the patterns of biomolecular and biochemical expression seen in subjects with spontaneously 
occurring EoE or other esophageal pathologies (historical controls). These control specimens 
will be obtained under separate protocols at the investigative laboratory.  
Criteria for Study Participation 
Inclusion Criteria 
Subjects who meet all of the following criteria are eligible for enrollment as study subjects: 
• 
Participation in the ARC004 study 
• 
Written informed consent from adult subjects 
• 
Written informed consent from parent/guardian for minor subjects 
• 
Written assent from minor subjects as appropriate (ie, above the age of 7 years) 
Exclusion Criteria 
Otherwise ineligible for ARC004 
Subject Termination from the Substudy 
After enrollment, subjects may withdraw consent from this substudy at any time. Subjects 
may also be withdrawn by the investigator for reasons of safety or compliance.  
Study Product  
No study product will be administered in the substudy.  
Study Procedures 
The following procedures will be performed:  
 Enrollment and Permissions  
• 
Obtain subject/parental signatures on IRB-approved informed consent/assent form. 
 Sample Collection, Handling, and Analysis Procedures 
• 
Saliva is the principal biospecimen to be collected in this study with the aid of a 
commercially available kit designed expressly for salivary RNA research purposes. 
Specific details for saliva collection will be provided to sites in a manual of 
procedures.  
• 
The results of blood samples for complete blood count, already collected in ARC004, 
will also be included in analyses relating to the secondary objectives of this substudy. 
• 
Biospecimens may be temporarily stored at investigational sites to facilitate batch 
shipping and receiving. All biospecimens will be packaged and transported to the 
investigative laboratory in a manner compliant with all local, state, and federal laws 

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and regulations, as per standard operating procedures of the shipping and receiving 
facilities. 
• 
Analyses will include 1 or more of the following:  
– 
Transcriptome analysis 
– 
EoE diagnostic panel comprising a 96-gene quantitative polymerase chain 
reaction (qPCR) array 
– 
Profiling of local cytokine expression  
– 
Targeted analysis of expression of previously identified specific candidate genes 
– 
Analysis of single nucleotide polymorphisms in previously identified specific 
candidate genes 
– 
Inflammatory pathway analysis (Ingenuity, Toppfun, or David) 
– 
qPCR analysis 
– 
Immunohistochemistry or other protein detection methods (eg ELISA, Western 
blot, etc.). 
– 
Mass spectrometry 
– 
Flow cytometry 
Lead Investigative Laboratory 
The lead investigative laboratory is the following: 
Wen Lab – Cincinnati Children’s Hospital Medical Center 
S6.405 S Building 
240 Albert Sabin Way 
Cincinnati, OH 45242 
USA 
 Safety Monitoring 
As the study entails no treatment, there can be no treatment-emergent or treatment-related 
AEs in this substudy. The principal risk associated with a genetic-based study is the potential 
for emotional reactions upon learning that the subject or a subject’s family member does or 
does not carry or express a gene associated with a particular condition. 
 Statistical Considerations 
This substudy is a pilot characterization of biochemical and biomolecular markers in relation 
to GI side effects arising during peanut OIT in ARC004 subjects. The analyses to be 
conducted in this substudy are all considered exploratory in nature. As such, descriptive 
statistical techniques will be utilized to characterize demographic and basic clinical variables, 
with standard assessments for normality and adjustments as necessary. Measures of 
correlation and longitudinal repeated measures will be assessed with appropriate techniques 
(eg, regression modeling) as necessary. Statistical testing for differences between treatment 
groups or time points may be assessed, but specific hypotheses are not pre-specified.  

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 Study Endpoint Assessment 
All endpoints in this study are considered exploratory and are defined in the 
Study Procedures section above.  
 Subject and Demographic Data 
Baseline Characteristics, Demographics, and Safety Data 
Baseline and demographic characteristics may be reported for each subject enrolled in the 
present study as they were obtained in ARC003 and ARC004. Baseline and demographic 
data could include age, race, sex, body weight, and height. Other analyses involving safety 
data may also be performed.  
Use of Medications 
There will be no medications used in this substudy. Data from concomitant medication use in 
ARC003 and ARC004 related to AEs may be analyzed as part of this substudy.  
 Sample Size Calculations 
This is an exploratory and hypothesis-generating study involving minimal risk to subjects. 
No specific sample size calculations have been performed.  

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Appendix 7: Longitudinally Applicable Exclusion Criteria 
Eligibility for ARC004 enrollment requires that the subject does NOT meet any of 
ARC003’s longitudinal exclusion criteria. These exclusion criteria are listed below: 
• 
History of cardiovascular disease, including uncontrolled or inadequately controlled 
hypertension (as described Section 5.10) 
• 
History of chronic disease (other than asthma, atopic dermatitis, or allergic rhinitis) 
that is, or is at significant risk of becoming, unstable or requiring a change in chronic 
therapeutic regimen 
• 
History of eosinophilic esophagitis (EoE) or other eosinophilic gastrointestinal (GI) 
disease 
• 
Current participation in any other interventional study other than ARC003 
• 
Subject is in “build-up phase” of immunotherapy to another allergen (ie, has not 
reached maintenance dosing) 
• 
Severe asthma (2007 National Heart, Lung, and Blood Institute [NHLBI] Criteria 
Steps 5 or 6, as described in 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: 
– 
Forced expiratory volume in 1 second (FEV1) < 80% of predicted, or ratio of 
FEV1 to forced vital capacity (FEV1/FVC) < 75% of predicted, with or without 
controller medications (only for age 6 years or greater and able to do spirometry) 
or 
– 
Inhaled corticosteroid (ICS) dosing of > 500 μg daily fluticasone (or equivalent 
ICSs based on NHLBI dosing chart) 
• 
History of steroid medication use (via intravenous [IV], intramuscular [IM], or oral 
administration) in any of the following manners:  
– 
history of daily oral steroid dosing for > 1 month during the past year or 
– 
2 burst oral (IM or IV) steroid courses, defined as ≥ 1 mg/kg of prednisone or 
prednisone equivalent, in the past year ≥ 1 week in duration 
• 
Inability to discontinue antihistamines 5 half-lives before the initial day of escalation, 
skin prick test (SPT), or double-blind, placebo-controlled food challenge (DBPCFC) 
• 
Lack of an available palatable vehicle food to which the subject is not allergic 
• 
Use of any therapeutic antibody (eg omalizumab, mepolizumab, reslizumab, etc.), 
any investigational peanut immunotherapy other than AR101 (eg, oral, sublingual, 
epicutaneous), or any other immunomodulatory therapy excluding corticosteroids 
within the past 6 months (Section 5.10)  
• 
Use of beta-blockers (oral), angiotensin converting enzyme (ACE) inhibitors, 
angiotensin receptor blockers (ARBs), or calcium channel blockers (as described 
Section 5.10).  
• 
Pregnancy or lactation 
• 
Having the same place of residence as another subject in the study 

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• 
Participation in another clinical trial, other than ARC003, within 30 days or 
5 half-lives of the investigational product, whichever is longer, prior to enrollment 
• 
Developing dose limiting symptoms in reaction to the placebo part of ARC003 
screening DBPCFC 
• 
History of a mast cell disorder, including mastocytosis, urticaria pigmentosa, and 
hereditary or idiopathic angioedema 
• 
Allergy to oat 
• 
Hypersensitivity to epinephrine and any of the excipients in the product