Immune Responses in Peanut Allergic Subjects Undergoing Peanut Oral Immunotherapy
Phase: PHASE1
Conditions: Peanut Allergic Subjects
Sponsor: Baylor College of Medicine

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Immune Cell Responses in Peanut Allergic Subjects Undergoing Peanut Oral 
Immunotherapy 
 
 
Coordinating Center: 
Baylor College of Medicine/Texas Children’s Hospital 
 
Principal Investigator (PI): Carla M. Davis, M.D. 
Pediatrics-Immunology, Allergy and Rheumatology 
1102 Bates Avenue, Suite MC330.01 
Houston, TX 77030-2399 
Telephone: 832-824-1440 
e-mail address: cmdavis@texaschildrens.org 
Sub-Investigators: 
 
    Sara Anvari, MD 
    Pediatrics-Immunology, Allergy and Rheumatology 
Telephone: 832-824-1319 
Email address: Sara.Anvari@bcm.edu 
 
    Kathleen Pitts, NP 
    Pediatrics-Immunology, Allergy and Rheumatology 
    Telephone: 832-824-1319 
    Email address: kpitts@bcm.edu     
 
    Aikaterini Anagnostou, MD 
    Pediatrics-Immunology, Allergy and Rheumatology 
    Telephone: 832-824-1319 
    Email address: Aikaterini.Anagnostou@bcm.edu 
 
    Sarah K. Nicholas, MD 
    Pediatrics- Immunology, Allergy and Rheumatology 
    Telephone: 832-824-1319 
    Email address: sknichol@bcm.edu 
 
Meera Gupta, MD 
    Pediatrics- Immunology, Allergy and Rheumatology 
    Email address: meera.gupta@bcm.edu 
 
Ashley Reiland, MSN 
    Pediatrics- Immunology, Allergy and Rheumatology 
    Email address: ashley.reiland@bcm.edu 
 
Melissa Hearrell, MSN, APRN, FNPC 
    Pediatrics-Immunology, Allergy and Rheumatology 
    Email address: melissa.hearrell@bcm.edu  
 

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Charles Minard, Ph.D. 
Biostatistician 
Telephone: 713-798-2353 
e-mail address:minard@bcm.edu 

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TABLE OF CONTENTS 
 
 
1. 
BACKGROUND AND RATIONALE ............................................................................... 3 
2. 
OBJECTIVES ................................................................................................................. 4 
2.1. 
Primary Objectives .............................................................................................................. 4 
2.2. 
Secondary Objectives .......................................................................................................... 5 
3. 
PATIENT ENROLLMENT CRITERIA ............................................................................. 5 
3.1. 
Inclusion Criteria ................................................................................................................. 5 
3.2. 
Exclusion Criteria ............................................................................................................... 6 
4. 
RECRUITMENT METHODS AND CONSENTING PROCESS .......................................... 6 
5. 
STUDY SCHEMA ........................................................................................................... 8 
6. 
TREATMENT/INTERVENTION PLAN ............................................................................... 9 
6.1. 
Screening Procedures .......................................................................................................... 9 
6.2. 
Study Medication/Intervention .......................................................................................... 10 
6.3. 
Entry Oral Food Challenge ............................................................................................... 11 
6.4. 
Buildup Visit Weeks 0 – 50 .............................................................................................. 13 
6.5. 
Follow-up Visits ................................................................................................................ 14 
6.6. 
0 Month Maintenance Study Food Challenge Visit (approximately 9 hours)…………….16 
6.7. 
End of Study Food Challenge Visits ................................................................................. 17 
6.8. 
End of Study Visit………………………………………………………………………..19 
6.9. 
Unscheduled Visits……………………………………………………………………….19 
6.10. Scientific Rationale for Immune Cell Response Studies ................................................... 19 
6.11. Correlative studies ............................................................................................................. 23 
6.12. Procedures for storing of extra or left over samples.......................................................... 23 
6.13. Criteria for Premature Termination of the Study (Stopping Rules) .................................. 23 
6.14. Participant Withdrawal Criteria ......................................................................................... 24 
6.15. Follow-up of Discontinued Participants ............................................................................ 25 
7. 
POTENTIAL RISKS AND DISCOMFORTS ................................................................... 28 
8. 
DATA MANAGEMENT ISSUES .................................................................................... 30 
8.1. 
Sources of Research Material ............................................................................................ 30 
8.2. 
Data and Safety Monitoring Plan ...................................................................................... 30 
8.3. 
Quality Assurance ............................................................................................................. 31 
9. 
MEASUREMENT OF EFFECT ...................................................................................... 31 
9.1. 
Response Review .............................................................................................................. 31 
9.2. 
Response Criteria .............................................................................................................. 31 
10. 
STATISTICAL CONSIDERATIONS .............................................................................. 32 
10.1. Sample size considerations ................................................................................................ 32 
11. 
PROTECTION OF HUMAN SUBJECTS ........................................................................ 33 
12. 
ADVERSE EVENTS ...................................................................................................... 34 
12.1. Adverse Event (AE) or Medical Event ............................................................................. 34 
12.2. Serious Adverse Event ...................................................................................................... 34 
12.3. Expected adverse event and unexpected adverse event..................................................... 35 
12.4. Toxicity Grading ............................................................................................................... 35 
12.5. Adverse Event Reporting .................................................................................................. 38 
12.6. Safety Reporting Requirements for IND Holders ............................................................. 38 
13. 
REFERENCES ...................................................................................................................40 
14. 
APPENDICES ................................................................................................................... 44 

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1. BACKGROUND AND RATIONALE 
 
Peanut allergy is a common condition and is increasing in prevalence, with 1-2% prevalence in 
the pediatric population.(1) There has been a doubling of the number of peanut allergic children 
during a recent 10 year period.(2) The natural history of peanut allergy is persistence with 
resolution in only about 20% of children.(3)  It is the most common cause of anaphylaxis in 
children presenting to the emergency room department.(4) 
 
Currently, the only treatment for peanut allergy is strict avoidance and, if unintentional ingestion 
occurs, treatment with medications to prevent food anaphylaxis is warranted.(3) Unfortunately, 
when accidental ingestion occurs, anaphylaxis and death can occur.(5,6)  Allergen avoidance 
affects the quality of life of the child and family, causes food related anxiety, and social 
limitation.  Although other allergic conditions like allergic rhinitis and asthma can be treated 
with subcutaneous allergen immunotherapy, this traditional therapy is not feasible in peanut 
allergy because of the significant risk of systemic side effects, like death from anaphylaxis.(7,8) 
 
Since subcutaneous immunotherapy to food is not feasible, oral immunotherapy trials have been 
performed with demonstrated safety and efficacy of this approach. Peanut allergy results from 
the breakdown of the immune system to maintain tolerance to peanut allergen. The gradual 
exposure to food proteins orally is thought to avoid acute allergic reactions by the induction of 
oral tolerance mechanisms like the production of inhibitory cytokines and regulatory T cells.(9- 
16) Desensitization, or a decreased clinical responsiveness to a defined amount of food allergen 
while consuming daily doses of the food, occurs through oral immunotherapy. Oral 
immunotherapy does not produce clinical tolerance of the food, defined as the ability to 
unrestricted amounts of the food antigen following a period of removal from daily dosing, but 
subjects are desensitized, defined as the ability to tolerate an increased amount of food without 
clinical symptoms after immunotherapy. 
 
The process of desensitization through immunotherapy occurs after an initial food challenge to 
determine what amount of food allergen causes a clinical reaction in the subject. There are two 
phases in treatment with oral immunotherapy. In the first phase, the build-up phase, the subject 
ingests gradually escalating doses of peanut flour, administered orally in a vehicle once every 
day with weekly or bi-weekly dose escalation.  Once a maintenance dose has been achieved, the 
subject continues to take this amount in a peanut equivalent dose over a period of years. Peanut 
equivalent dosing has been used in several prior peanut OIT trials without report of increased 
side effects or adverse events. (17-20) The peanut flour manufacturer for the initial trials in 
peanut oral immunotherapy by centers in the Consortium of Food Allergy Research (CoFAR) 
only provided dosing for the buildup phase for the trials and peanut equivalent dosing was used 
by centers for the maintenance phase. (Personal communication) Therefore, given the experience 
with peanut equivalent dosing, after the first year of this study, patients will be switched to a 
daily peanut equivalent dose and intake will be monitored by daily diaries. Since the daily dose 
will still be 3900 mg of peanut protein for the maintenance phase, the immunologic effects of the 
peanut dosing are not likely to be affected. (11, 12) 
An open label study with an initial dose of 100 µg increased to 300 mg maintenance dose for 
several months demonstrated efficacy in over 90% of the subjects with desensitization and 
tolerance of a 3900 mg dose on food challenge.(11,12) A follow up double blind study 

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demonstrated efficacy with treated subjects tolerating 5000 mg compared to 280 mg in placebo 
subjects. The safety analysis of these studies demonstrated that 93% of children experienced 
symptoms on initial dosing day with 15% requiring epinephrine.(9) Most reactions were mild. 
However, when the initial dose was decreased from 50 mg down to 6 mg, allergic side effects 
were noted in only 47%.  Of 10,184 home maintenance dosings of peanut flour, only 3.5% 
caused symptoms, with 2 subjects receiving epinephrine, each after one maintenance dose 
(0.02%). The relative safety of this approach has been demonstrated in these initial trials.(9) 
 
Given the risk of clinical reactions to peanut allergen with accidental unintentional exposures 
and the impact of peanut avoidance on the quality of life of peanut allergic subjects (21), peanut 
immunotherapy as an effective treatment is an unmet need. This effective therapeutic procedure 
with an acceptable safety profile is needed in more academic centers around the country. 
Subjects receiving this therapy need close monitoring through expert centers to treat potential 
systemic symptoms.  The immune determinants of clinical tolerance are still not completely 
understood. The goal of this proposed trial is to utilize the efficacy of oral immunotherapy to 
study the safety of peanut oral immunotherapy and evaluate immune mechanisms of clinical 
tolerance, using technology to identify T cell cytokine responses and subsets by flow cytometry. 
This trial will also expand the availability of this therapy to subjects in the southern United 
States. 
 
All subjects will receive the peanut protein intervention. There is no placebo control for this 
study. In order to meet inclusion criteria subjects will not be able to tolerate a 1 gram peanut 
protein challenge. The primary outcome to be studied is the safety of the therapy and the 
secondary outcome will include changes in T and NKT cell function and intracellular cytokine 
expression from peanut allergic subjects during peanut OIT. We will look at both the initial 
response to building up the dose and changes during the maintenance phase. We are requesting a 
target enrollment of 15 subjects. Subjects will be recruited from the Texas Children's Hospital 
Allergy and Immunology Clinic. Subjects are expected to participate for a total of 38 months. 
After screening visits, the study will require approximately 33 visits with 2 phases: the build-up 
phase (weeks 0-50), followed by the maintenance phase (2 years). 
 
 
2. OBJECTIVES 
2.1 
Primary Objectives: 
 
2.1.1. The primary objective is to determine whether peanut oral immunotherapy safely 
develops clinical tolerance in peanut allergic patients by assessing the change of dose 
tolerated and to determine the percentage of subjects who can tolerate 6 g of peanut 
flour with absence of clinical symptoms during a food challenge following the initial 
desensitization phase of peanut flour which includes a 50 week dose escalation phase 
and 104 week maintenance phase on a peanut equivalent dose. 

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2.1.  Secondary Objectives: 
 
To determine the immune mechanisms of clinical tolerance, using technology to identify 
T cell cytokine responses and subsets, as well as basophil activation responses as 
measured by flow cytometry. T and NKT cell function and intracellular cytokine 
expression will be measured. 
 
2.2.1. 
To determine whether viral exposure potentiates response to in vitro peanut 
allergen exposure and to assess those changes during peanut OIT. 
 
2.2.2. 
To compare the change in dose tolerated after one month of abstaining from 
peanut to determine sustained unresponsiveness. 
 
 
3. PATIENT ENROLLMENT CRITERIA 
 
 
3.1. 
Inclusion Criteria: 
 
Subjects who meet all of the following criteria are eligible for enrollment as study 
participants: 
 Age 5-16 years of either sex, any race, any ethnicity, weighing at least 18.3 kg at the time 
of the initial visit. 
 The presence of IgE specific to peanuts (a positive skin prick test to peanuts (diameter of 
wheal >3.0 mm) and a positive in vitro IgE [CAP-FEIA] > 7 kU/L). 
 Significant clinical symptoms occurring within 120 minutes after ingestion of the last 
tolerated dose of peanut protein during the DBPCFC. Patients who have not had previous 
oral exposure to peanut will be observed for a longer duration of 150 minutes because 
they may demonstrate a delayed immune response, given the lack of prior peanut 
exposure. Also, patients with a history of prior anaphylaxis will be observed for 150 
minutes. (21-24) 
 Provide signed informed consent. 
 Ability to follow-up regularly for scheduled appointments. 
 Subjects will not be excluded if they are primarily Spanish speaking. 
 Females of childbearing potential must be willing to practice an acceptable form of birth 
control throughout the protocol. 
 Epinephrine injection training provided 
 Participant has current in-date epinephrine injector and parent/guardian demonstrates 
proper use. 

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3.2. Exclusion Criteria 
 
Subjects who meet any of the following criteria are not eligible for enrollment as study 
participants: 
 History of severe anaphylaxis to peanut as defined by hypoxia, hypotension, or 
neurological compromise (Cyanosis or SpO2 < 92% at any stage, hypotension, 
confusion, collapse, loss of consciousness; or incontinence) 
 Currently participating in a study using an investigational new drug. 
 Participation in any interventional study for the treatment of food allergy in the past 12 
months or while participating in this study. 
 Poor control or persistent activation of atopic dermatitis. 
 Diagnosis of persistent asthma as defined by NHLBI criteria and currently being treated 
with daily doses of inhaled corticosteroids or requiring a rescue inhaler more than 2 days 
per week. 
 Inability to discontinue antihistamines for skin testing and Oral Food Challenges (OFCs). 
 Pregnant female. 
 Chronic medical condition requiring frequent use of oral steroids, chronic psychiatric 
illness or history of substance abuse. 
 Active eosinophilic esophagitis requiring medication therapy during the past 12 months 
 Subjects with known oat or wheat allergy 
 Subjects currently on the build-up phase of environmental allergy immunotherapy 
injections 
 
Live more than 175 miles away from Texas Children’s Hospital located in the Medical 
Center. 
 
NOTE: 
Treatment of glucocorticoids (i.e. prednisone, methylprednisolone, and prednisolone) is 
permitted while on the study for subjects with wheezing and/or undiagnosed asthma.  The 
dosing allowed will be no more than 2 mg/kg up to 21 days. Subjects will be taken off the 
study if treatment with any dose of steroid is required for greater than 21 days or if oral 
systemic corticosteroids are required greater than twice per year for asthma exacerbations. 
 
4. RECRUITMENT METHODS AND CONSENTING PROCESS 
 
Subjects meeting criteria for participation in the study will be recruited from Dr. Davis’s clinic at 
Texas Children's Hospital, Allergy and Immunology Section.  They will be informed of the 
consent procedure and study details as outlined in this document. 
 
Subjects that are not patients of Dr. Davis will be recruited by referral from other Allergy and 
Immunology physicians within Texas Children's Hospital and by referral from community 

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physicians. Physicians in the community will learn about the study by word of mouth or by 
talking with Dr. Davis and will ask their patients to contact Dr. Davis or their staff directly. 
Printed materials will not be used to recruit subjects and subjects not seen by Dr. Davis will not 
be contacted by Dr. Davis or their staff directly for recruitment purposes.  Details of the study 
including inclusion criteria and exclusion criteria will be discussed with prospective subjects 
when they contact Dr. Davis or their staff. We will target underrepresented patients for 
enrollment to reflect the patient pool diversity. 
 
Consent will be required from a parent or legal guardian of all study subjects and will be 
documented in the research records.  Subjects will be consented in a private location by study 
personnel.  Measures will be taken to minimize undue influence or coercion. Assent will be 
required of all minor subjects 7 years of age and over. 
 
This protocol is be registered on ClinicalTrials.gov. 

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Build Up Phase: Week 0-50 
See Dosing Schedule Below 
 
 
 
5. STUDY SCHEMA 
 
 
 
 
 
 
 
 
Maintenance Phase: 
3.9 gm protein or highest 
achieved dose 
24 months 
Food Specific IgE 
OFC 6 gm 
 
For all still on 
therapy, withdraw for 
~ 4 weeks and OFC 
6gm 
 
 
DBPCFC 
DBPCFC 
DBPCFC 
 
 
 
 
 
- Indicates lab studies 
 
 
 
 
 
Treatment 
Maintain 3.9 gm or highest dose achieved 
6 
w 
1
2
1
8
2
4
3
0
3
6
4
2
4
8
Screening 
DBPCFC 
6, 12, 18, 24, 30, 36, 42, and 48 
weeks of build-up phase 
0 
m 
6 
m 
1
2
1
8
2
4
2
5
Week – 4: discontinue oral steroids 
Week – 1: discontinue 
antihistamines 
End of 
Study 

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6. TREATMENT/INTERVENTION PLAN 
 
The study will require approximately 36 visits over approximately 40 months. Subjects will 
come to Texas Children's Hospital in Houston, TX for all desensitization procedures. Subjects 
will discontinue antihistamines (for example, Benadryl or Claritin) for 7 days before the first 
visit for the entry food challenge and the initial dose escalation. Dose escalation means to give 
a larger amount of study protein than the subject was previously taking.  Each time the dose is 
increased the subject will need to come to Texas Children's Hospital in Houston, TX to be 
observed. Subjects may take antihistamines during the study but must stop them one week prior 
to the first visit for the entry food challenge. Once 3900 mg of peanut protein or highest 
tolerated dose is achieved, the subject will switch to a peanut equivalent dose for the 
maintenance phase. 
Subjects must be off oral corticosteroids (for example, Prednisone) within one month of the 
procedure but they may be taken during the remainder of the study if needed. For the subjects 
safety prior to any food challenge an IV catheter needle will be inserted into a vein in the 
subject’s arm in case medications are needed for treatment of a reaction. EMLA® cream or L-M- 
X®, a medicine put on the skin to numb it, may be applied to the skin prior to IV placement to 
make it less painful. 
The subject will have blood drawn throughout the study. Approximately 1-2 teaspoons will be 
drawn at the screening visit and 4 to 6 tablespoons will be drawn approximately every 6 weeks 
during the first year and every 6 months during the second and third years. The total amount of 
blood for the entire study will be from 60-90 tablespoons. 
 
 
6.1. Screening Procedures: 
 
This visit should take approximately 3 hours. 
The following information will be collected: 
 Consent and assent; 
 Physical exam and medical and diet history; 
 Vital signs (pulse, respiratory rate, blood pressure, weight, height, temperature); 
 Blood tests (1 teaspoon to measure peanut-specific IgE); 
 Allergy skin prick tests (A small amount of allergen dissolved in solution is placed on the 
skin, and the skin is scratched allowing the solution to enter the skin. The presence of a 
wheal indicates sensitivity to the allergen. The subject will experience itching at the site 
of the procedure if they are sensitized to peanut. The starting concentration will be the 
standard peanut extract 1:20 wt/vol with serial dilutions of 1:200, 1:2000, 1:20,000, and 
1:200,000 wt/vol as well as oat, wheat, positive (histamine) and negative (saline) 
controls.) 
 Demographic information (age, sex, ethnic origin). 
 Serum pregnancy test for menstruating females (1/10 tsp of blood) 

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 Spirometry:  Spirometry will be attempted in all participants.  If valid spirometry results 
are not successfully obtained, the attempt is documented and peak flow measures will be 
accepted for the entry criteria with results >90% of predicted.  For participants that are 
able to complete spirometry, FEV1 must be greater than 90% predicted. 
 Peak flow will be determined for the patient. 
 Screening visit will occur within 1 month of the DBPCFC. 
 
 
6.2. 
Study Medication/Intervention: 
 
The product to be used in this study is only peanut flour. Subjects that cannot tolerate the initial 
low doses of peanut flour will not be enrolled. The peanut flour will be given in small pre- 
measured soufflé cups containing the amount of peanut flour that needs to be eaten for one dose. 
The flour will be received from the University of North Carolina at Chapel Hill Manufacturing 
Facility (See Letter of Authorization). Lot-to-lot testing will be performed by the manufacturer 
on each batch of new peanut flour to ensure accuracy of dosing potency. The process involves 
running an SDS-PAGE gel with the previous lot and the new lot. Densitometric scanning is then 
performed to compare Ara h 1 levels and Ara h 2 levels. The University of North Carolina at 
Chapel Hill Manufacturing Facility has defined the acceptable ranges to be less than 30% for Ara 
h 1 and 20% for Ara h 2. If a lot fails the test, the batch is discarded and a new lot of peanut flour 
is ordered. The peanut protein will be received by the Center for Cell and Gene Therapy at 
Baylor College of Medicine (CAGT). 
The CAGT is a Good Manufacturing Practice (GMP) compliant facility (See Letter of 
Authorization) and is accredited by the Foundation for the Accreditation of Cellular Therapy 
(FACT), the College of American Pathologists (CAP) and is CLIA registered. The protein doses 
will be monitored and dispensed by the CAGT GMP Facility. 
The drug would be stored in the cold room (2-8°C) within the clean room area restricted to 
CAGT GMP Facility Staff. It is on continuous temperature monitoring via our Isensix system. In 
the case of an alarm staff is informed via pager system. Alarms and monitoring data are also full 
backed up by Isensix in San Diego. This drug will be stored in a dedicated facility away from 
other allergens and will be handled in a separate room on a separate air handling systems. 
The pre-measured soufflé cups will be transported by a clinical research staff member within 
Texas Children’s Hospital controlled environment. 
The peanut flour will be used within the manufacturer’s expiry date and our center will follow all 
instructions provided by the manufacturer. 
One dose of peanut flour is taken per day. Prior to taking the dose the subject must eat a snack 
high in carbohydrate and fat such as a bagel or chips and then eat the peanut flour mixed into 
liquid or another food such as apple sauce or ice cream. 
The vehicle food for each subject will be a food, to which the subject is not allergic. The subject 
will need to eat the peanut flour at approximately the same time every day.  After eating the 
peanut flour the subject will need to be with a supervising adult for the next 2 hours so they can 
monitor for any possible reaction.  The subject cannot go to school within 2 hours of eating the 

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peanut flour and cannot go to bed within 2 hours of eating the peanut flour. After 1 month, if 
there are no adverse events with the maintenance dose or highest dose tolerated, the provider will 
have the option of decreasing the observation period to 1 hour with no physical activity to occur 
for 1 hour. 
Subjects who miss one to two days of the daily dose will continue at their present dose. Those 
who miss 3 to 4 days of the daily dose of study product will receive their next dose at the Allergy 
and Immunology Clinic and be observed for a minimum of 2 hours after dosing to assure safety 
with dosing.  Those who miss more than 4 days will return to the Allergy and Immunology 
Clinic for a graded challenge. The subject will switch to a peanut equivalent dose once he/she 
reaches the maintenance dose or highest dose achieved. 
 
 
The dosing guidelines for peanut flour will continue to be followed. 
 
Table 1. Schedule during build-up phase for missed daily doses 
(time intervals from missed doses) 
• Up to 2 days, continue doses as scheduled. 
• 3-4 consecutive days after missed dose; repeat previous doses but dose will be given in 
the Allergy/Immunology Clinic. 
• More than 4 days after missed dose, patient will return to Allergy/Immunology Clinic 
for a graded challenge. 
 
6.3. Entry Oral Food Challenge (approximately 9 hours): 
 
 Amount of blood to be drawn at this visit:  Blood drawn to check the peanut-specific IgE, 
IgG and IgG4 levels,  and cellular immune studies and basophil activation studies will be 
drawn and evaluated at Texas Children’s Center for Human Immunobiology (Baylor 
College of Medicine) for analysis. 
IgG and IgG4 are antibodies that may have a role in tolerating peanut.  They will be 
followed throughout the study and we will evaluate how they are changing while the 
subject is on therapy. In addition we will be obtaining blood for the immune cell studies. 
 In order to obtain sufficient quantity of cells we will collect the maximum amount of 
blood allowable as defined by Texas Children’s Hospital based on the subject’s weight. 
This will range from 4 to 6 tablespoons total of blood drawn for the visit. 
 Spirometry: Spirometry results or peak flow measures will be accepted. For participants 
that complete peak flow the results must be > 90% of predicted.  For participants that 
complete spirometry, FEV1 must be greater than 90% predicted on the day of the 
challenge to participate in the food challenge. 
 Targeted History and Physical Exam and Diet History: A brief medical and diet history 
will be obtained and a focused physical exam will be performed. 

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 DBPCFC:  Subjects eligible for the study (peanut-specific immunoglobulin E level 
greater than 7kU/L AND a positive skin prick test to peanut) will come to Texas 
Children's Hospital in Houston for a Double Blind Placebo Controlled Food Challenge 
(DBPCFC) to the study protein to determine if the subject is allergic to peanut. The table 
below labeled Table 2 details dosing for the initial DBPCFC and also shows the dose at 
which the subject will start treatment correlating with the dose at which a reaction is 
noticed. 
 
 
Table 2. Entry Double-Blinded Placebo Controlled Food Challenge Protocol and 
Starting Dose of Oral Immunotherapy to be Initiated 
Dose Number 
Approximate 
Dose Weight 
(PEANUT 
FLOUR) 
Approximate 
Dose Weight 
(PEANUT 
PROTEIN) 
Cumulative 
Dose Weight 
(peanut protein) 
Starting 
Dose of OIT 
if Subject 
Reacts 
1 
1 mg 
0.5 mg 
0.5 mg 
Ineligible 
2 
2 mg 
1 mg 
1.5 mg 
Ineligible 
3 
10 mg 
5 mg 
6.5 mg 
1.8mg 
4 
30 mg 
15 mg 
21.5 mg 
3.6 mg 
5 
108 mg 
54 mg 
75.5 mg 
14.4 mg 
6 
150 mg 
75 mg 
150.5 mg 
28.8 mg 
7 
200 mg 
100 mg 
250.5 mg 
40 mg 
8 
500 mg 
250 mg 
500.5 mg 
120 mg 
9 
1000 mg 
500 mg 
1000.5 mg 
300 mg 
10 
2000 mg 
1000 mg 
2000.5 mg 
750 mg 
 
The DBPCFC visit will last approximately 9 hours. The food challenge may be performed in one 
day or split into two days. The subject will discontinue antihistamines (for example Zyrtec or 
Claritin) for 7 days before the procedure and must be off oral corticosteroids for one month 
before the food challenge. 
A DBPCFC consists of eating both a food to which the subject may be allergic (peanut) and 
eating a placebo at different times. A placebo is a substance that is similar to the test substance in 
appearance, smell, and taste. The peanut protein is a flour and will be given mixed with either 
juice (at lower doses) or with a food like baby food. The placebo is oat flour for peanut 
DBPCFC and will be given in the same manner. 
The food will be given in a “double-blinded” fashion under observation at Texas Children's 
Hospital in Houston. During both of the feedings, the food protein to be given during the 
challenge will start with the equivalent of less than 1/100th of a peanut and progressively larger 
doses will be given at 15 minute intervals if the subject does not have an allergic reaction to one 
of the doses. If the subject does have a reaction to one of the doses, the dosing of study protein 
will be stopped and the allergic reaction will be treated with an antihistamine and/or epinephrine 
or other emergency medications which may include but is not limited to bronchodilators, oral or 
injectable steroids, or H2 blockers). Overall, patients with a history of a prior clinical reaction to 
peanut will be observed for 120 min after ingestion of the last tolerated dose of peanut protein 
during the DBPCFC. Patients who have not had previous oral exposure to peanut may 

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demonstrate a delayed immune response, given the lack of prior peanut exposure. Therefore, 
those subjects will be observed for a longer duration of 150 minutes. (21-24) The highest dose of 
peanut protein will be equivalent to 4 peanuts. The initial dose of therapy will be determined by 
the provider and will be slightly lower than the amount at which the subject reacted to during the 
DBPCFC (Table 2). 
 
 
6.4. Buildup Visit Weeks 0 – 50 or until highest tolerated dose (maintenance dose) is 
reached (approximately 3 hours per visit): 
 
 First build-up visit will occur within 1 month of the DBPCFC. If the subject has 
symptoms with the first home dose in the clinic, the child may return for a lower dose 
visit up to two times. If he/she cannot tolerate the 1.8mg dose, the subject will be 
excluded from the trial. 
 Amount of blood to be drawn:  Every 6 weeks at weeks 6, 12, 18, 24, 30, 36, 42, 48, etc. 
we will draw up to 4-6 tablespoons of blood (based on the subject’s weight) for immune 
studies, peanut-specific IgE, IgG, and IgG4 and basophil histamine release assays. Blood 
will not be drawn at the other build-up visits. 
 Peak Flow:  Peak flow measures will be accepted with results >90% of predicted. 
 Allergy Skin Prick Tests: At week 24, endpoint dilution skin testing to peanut will be 
repeated. The procedure will be performed as described under section 6.1 “Screening 
Procedures.” 
 Targeted History and Physical Exam and Diet History: A brief medical and diet history 
will be obtained and a focused physical exam will be performed. 
 Review Home Symptom Diary:  At each visit we will review any symptoms experienced 
while taking the food protein. 
 Epinephrine injector will be checked for expiration date and parents/guardian will 
demonstrate proper use. 
 Dose Escalation: The subject must return in no less than 10 days after each visit to 
receive an increased amount of peanut protein. (See Table 3.)  At each visit the subject 
will be given a slightly larger amount of peanut protein than he or she was receiving prior 
to that visit.  After the first visit the subject will be taking at least the equivalent of 
approximately 1/100th of a peanut daily and once the subject gets to the maintenance 
dose he or she will be taking the equivalent of approximately 15 peanuts daily. The 
length of time the participant is in the build-up phase is dependent on the starting dose 
determined from DBPCFC and how well each subsequent buildup dose is tolerated. The 
subject will build up to 3.9 grams of peanut protein or the highest dose tolerated. This is 
known as the maintenance dose. 

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Table 3. Dose Escalation Table 
 
Weeks 
On 
OIT 
Dose 
No. 
Protein Per 
Soufflé 
portion cup 
(mg) 
PN flour 
weight per 
soufflé 
portion cup 
(mg) 
0,1 
1 
1.8 
3.6 
2,3 
2 
3.6 
7.2 
4,5 
3 
7.2 
14.4 
6,7 
4 
14.4 
28.8 
8,9 
5 
28.8 
57.6 
10,11 
6 
40 
80 
12,13 
7 
60 
120 
14,15 
8 
80 
160 
16,17 
9 
100 
200 
18,19 
10 
120 
240 
20,21 
11 
240 
480 
22,23 
12 
300 
600 
24,25 
13 
450 
900 
26,27 
14 
600 
1200 
28,29 
15 
750 
1500 
30,31 
16 
900 
1800 
32,33 
17 
1050 
2100 
34,35 
18 
1200 
2400 
36,37 
19 
1350 
2700 
38,39 
20 
1500 
3000 
40,41 
21 
1800 
3600 
42,43 
22 
2100 
4200 
44,45 
23 
2400 
4800 
46,47 
24 
3000 
6000 
48,49 
25 
3600 
7200 
50,51 
26 
3900 
7800 
 
 
 
6.5. Follow-up Visits (every 6 months for 24 months after maintenance dose is 
reached) (approximately 3 hour per visit): 
 
Once the maintenance dose is achieved, the patient will follow up in the clinic 2 weeks 
later to ensure the higher dose is being tolerated and will switch to a peanut equivalent 

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dose (Table 4). The first dose of the peanut equivalent will be given in the hospital 
setting. The family will be instructed on how to administer peanut equivalent dose. The 
subject will continue to follow the “Instructions for Daily Home Doses” as used for 
peanut flour dosing. This will be considered “Month 0”. The participant will remain on 
this dose for 24 months and follow-up visits will occur every 6 months. The subject will 
continue to follow the peanut flour dosing guidelines. A food challenge will be performed 
within 1 month of the “Month 0” visit. 
 
 
Table 4. Peanut Equivalent Dose 
 
 
Peanut Product 
Peanut Protein (gram) 
/serving 
Maintenance 
Dose 
(3900mg peanut 
protein) 
Alternative 
Dose 
(if maintaining 
below 3900mg) 
Creamy Peanut Butter 
*Peter Pan or Reese’s 
Creamy Peanut Butter* 
8 grams=2 Tablespoons 
1 Tablespoon 
1300 mg =1 
teaspoon 
325mg=0.25 
teaspoon 
JIF Peanut Powder 
8 grams=3 Tablespoons 
1.5 Tablespoons 
PB2 Powdered Peanut 
Butter (Bell Plantation) 
5 grams=2 Tablespoons 
1.5 Tablespoons 
1300 mg= 1.5 
teaspoon 
300 mg = 3/8ths 
of a teaspoon 
Dry Roasted Peanuts 
0.175 grams=1 peanut 
22 peanuts 
1300 mg = 7 
and ½ peanuts 
350 mg = 2 
peanuts 
Peanut M&M’s 
0.15 grams=1 piece 
26 pieces 
1300 mg = 8 
and 2/3 pieces 
300 mg=2 
pieces 
Reese’s Pieces Candy 
0.078 grams=1 piece 
50 pieces 
1300 mg = 16 
and 2/3 pieces 
312 mg = 4 
pieces 
Reese’s Peanut Butter Cups 
Miniatures 
0.8 grams=1 miniature cup ̴5 miniature cups 
1300 mg = 1 
and 5/8th cups 
300 mg = 3/8th 
cup 

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Other approved alternative: 
 
 
 
 If the subject experiences no adverse events with the maintenance dose or highest dose 
tolerated after 1 month, the provider will have the option of decreasing the observation 
period at home to 1 hour. The subject will need to avoid any form of physical activity 2 
hours after ingestion. 
 Peak Flow: Peak flow measures will be accepted with results >90% of predicted. 
 Amount of blood to be drawn: After maximum tolerated dose is achieved at 
approximately 1 year (drawn at Visit 30- Month 0 DBPCFC) and every 6 months 
afterwards, we will draw up to 4-6 tablespoons of blood (based on the subject’s weight) 
for peanut-specific IgE, IgG, and IgG4, cellular immune studies and basophil histamine 
release assays until the end of the protocol. 
 Allergy Skin Prick Tests (PST):  Endpoint dilution skin testing to peanut will be done at 
month 0 and month 12 visits. 
 Targeted History and Physical Exam and Diet History: A brief medical and diet history 
will be obtained and a focused physical exam will be performed. 
 Epinephrine injector will be checked for expiration date and parent/guardian will 
demonstrate proper use. 
 Review Home Symptom Diary:  At each visit we will review any symptoms experienced 
while taking the food protein. 
 Administer Peanut Equivalent Dose: The first dose of the peanut equivalent will be given 
in the hospital setting followed by a 2 hour observation period. 
 Urine Pregnancy Test:  For females of reproductive potential a urine pregnancy test will 
be performed at month 0 and month 12 visits. If the subject is pregnant she will be 
dismissed from the study. 
 
6.6. 0 Month Maintenance Study Food Challenge Visit (approximately 9 hours) 
 The food challenge will need to be completed within 1 month of the “Month 0” visit. 
 Amount of blood to be drawn:  At this visit, we will draw up to 4-6 tablespoons of blood 
(based on the subject’s weight) for peanut-specific IgE, IgG, and IgG4 and cellular 
immune studies, and basophil histamine release assays 
 Spirometry or Peak Flow: Spirometry will be attempted in all participants.  If valid 
spirometry results are not successfully obtained, the attempt is documented and peak flow 
measures will be accepted for the entry criteria with results >90% of predicted. For 
participants that are able to complete spirometry, FEV1 must be greater than 90% 
predicted on the day of the challenge to participate in the food challenge. 

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 Targeted History and Physical Exam and Diet History: A brief medical and diet history 
will be obtained and a focused physical exam will be performed. 
 DBPCFC:  The subject will come to Texas Children's Hospital in Houston for a Double 
Blind Placebo Controlled Food Challenge (DBPCFC) to the study protein (peanut) to 
determine if he or she is still allergic to peanut or can tolerate peanut. 
The DBPCFC visit will last approximately 9 hours. The food challenge may be 
performed in one day or split into two days. The subject will discontinue antihistamines 
(for example Zyrtec or Claritin) for 7 days before the procedure and must be off oral 
corticosteroids for one month before the food challenge. 
Peanut equivalent will be used for the food challenge at 0 month maintenance food 
challenge. The challenge will consist of increasing doses of peanut (in the form of peanut 
equivalent) given every 15 minutes in increasing amounts (Table 5). The other 
challenge will consist of placebo material given also in increasing doses.  The highest 
dose will be equivalent to approximately 34 peanuts. 
 Review Home Symptom Diary: We will review any symptoms experienced while taking 
the food protein. 
 Urine Pregnancy Test:  For females of reproductive potential a urine pregnancy test will 
be performed prior to the food challenge.  If the subject is pregnant the food challenge 
will not be performed and the subject will be dismissed from the study. 
 
 
Table 5 
 
0 Month Maintenance Phase Double-Blinded Placebo 
Controlled Food Challenge Protocol 
Dose Number 
Approximate 
Dose Amount 
(PEANUT 
PROTEIN) 
Cumulative Dose 
Amount (peanut 
protein) 
1 
75 mg 
75 mg 
2 
150 mg 
225 mg 
3 
500 mg 
725 mg 
4 
1000 mg 
1725 mg 
5 
2000 mg 
3725 mg 
6 
3000 mg 
6725 mg 
7 
4000 mg 
10725 mg 
8 
4500 mg 
15225 mg 
9 
5000 mg 
20225 mg 
10 
6000 mg 
26225 mg 
 
 
6.7. End of Study Food Challenge Visits (24 and 25 months after maintenance dose is 
reached) (approximately 8 hours per visit): 

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 Amount of blood to be drawn:  At both visits, we will draw up to 4-6 tablespoons of 
blood (based on the subject’s weight) for peanut-specific IgE, IgG, and IgG4, cellular 
immune studies, and basophil histamine release assays 
 Allergy Skin Prick Tests (PST): Endpoint dilution skin testing to peanut will be done at 
the month 24 and month 25 visit. 
 Spirometry or Peak Flow: Spirometry will be attempted in all participants.  If valid 
spirometry results are not successfully obtained, the attempt is documented and peak flow 
measures will be accepted for the entry criteria with results >90% of predicted. For 
participants that are able to complete spirometry, FEV1 must be greater than 90% 
predicted on the day of the challenge to participate in the food challenge. 
 Targeted History and Physical Exam and Diet History: A brief medical and diet history 
will be obtained and a focused physical exam will be performed. 
 DBPCFC:  The subject will come to Texas Children's Hospital in Houston for a Double 
Blind Placebo Controlled Food Challenge (DBPCFC) to the study protein (peanut) to 
determine if he or she is still allergic to peanut or can tolerate peanut. 
The DBPCFC visit will last approximately 9 hours. The food challenge may be 
performed in one day or split into two days. The subject will discontinue antihistamines 
(for example Zyrtec or Claritin) for 7 days before the procedure and must be off oral 
corticosteroids for one month before the food challenge. 
Peanut equivalent will be used for the food challenge. The challenge will consist of 
increasing doses of peanut (in the form of peanut flour and mixed with juice or baby 
food) given every 15 minutes in increasing amounts (Table 6). The other challenge will 
consist of placebo material given also in increasing doses. The highest dose of peanut 
flour will be equivalent to approximately 34 peanuts. 
They will return 4 weeks after the 24 month food challenge for the 25 month food 
challenge. It will be conducted in the same manner as the 24 month food challenge. 
During this 4 week interval the subject must avoid peanut in his or her diet and will not 
take any peanut protein as he or she had been doing previously. 
 Review Home Symptom Diary:  At the 24 month visit we will review any symptoms 
experienced while taking the food protein. 
 Urine Pregnancy Test:  For females of reproductive potential a urine pregnancy test will 
be performed prior to the food challenge at both the 24 month and 25 month visits.  If the 
subject is pregnant the food challenge will not be performed and the subject will be 
dismissed from the study. 
 
 
 
Table 6. 
 
 
24 and 25 Month Maintenance Phase Double-Blinded 
Placebo Controlled Food Challenge Protocol 

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Dose Number 
Approximate 
Dose Weight 
(PEANUT 
PROTEIN) 
Cumulative Dose 
Weight (peanut 
protein) 
1 
75 mg 
75 mg 
2 
150 mg 
225 mg 
3 
500 mg 
725 mg 
4 
1000 mg 
1725 mg 
5 
2000 mg 
3725 mg 
6 
3000 mg 
6725 mg 
7 
4000 mg 
10725 mg 
8 
4500 mg 
15225 mg 
9 
5000 mg 
20225 mg 
10 
6000 mg 
26225 mg 
 
 
 
6.8 End of Study Visit 
 Peak Flow:  Peak flow measures will be accepted with results >90% of predicted. 
 FAQLQ/FAIM Questionnaire 
 Targeted History and Physical Exam and Diet History: A brief medical and diet history 
will be obtained and a focused physical exam will be performed. 
 Review Home Symptom Diary:  At each visit we will review any symptoms experienced 
while taking the food protein. 
 Epinephrine injector will be checked for expiration date and parents/guardian will 
demonstrate proper use. 
 Dose Administration: The subject must return within 7 days from the food challenge to 
receive the exit maintenance dose using peanut equivalent. The dose will be determined 
based on the investigator’s clinical judgment. If the subject is unable to tolerate the dose, 
he/she may return for a repeat visit. 
 
6.9 Unscheduled Visit 
Subjects may return to the site at any time throughout the study duration at the provider’s 
discretion for additional evaluation if there are concerns of an adverse reaction. The 
procedures performed at unscheduled visits may include any or all of those performed at the 
build-up visits as well as spirometry. The procedures performed will be at the provider’s 
discretion.  
6.10 Scientific Rationale for Immune Cell Response Studies: 
 
Peanut allergy has more than tripled in prevalence over the past decade, and there are no reliable 
predictors of peanut allergic reactions. This provides the impetus to conduct research to 
characterize the mechanistic factors driving the immune responses and evaluate the effect of T 
and NK T lymphocyte phenotypic and functional profiles in the development of tolerance to 

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peanut. A novel experimental polyfunctional flow cytometric method will be utilized. This 
research will address major deficiencies in the current knowledge regarding the effect of T and 
NK T lymphocyte activation and cytokine production in peanut allergic populations. 
 
This approach will help elucidate the complex immune mechanisms involved in the expression 
of allergic inflammation in vivo in anaphylaxis.  T cells are recognized to play a key role in the 
inhibition of adaptive immune responses through regulatory mechanisms in food allergic disease. 
Hence, a better characterization of surface and intracellular Th1, Th2, NKT and T regulatory 
responses will elucidate mechanistic pathways for maintenance of homeostasis. 
 
Furthermore, the blood samples collected will be used to perform basophil histamine release 
assays in order to analyze basophil activation in the participants undergoing OIT.  Recent studies 
have suggested that basophil activation was positively correlated with DBPCFC severity scores 
and that testing could discriminate between allergic and non-allergic subjects, thus serving as an 
additional tool to predict clinical severity.(22) 
 
The specific aim is to define the role of peanut specific T cell responses on the regulation of 
tolerance in peanut allergic disease.  The relationship between the level of tolerance (i.e. highest 
clinically tolerated peanut protein dose) and peanut specific T cell activation markers, 
transcription factors and intracellular inflammatory cytokine production will be further 
characterized.  Furthermore, we will analyze basophil activation in subjects undergoing OIT. 

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Hypothesis: Polyfunctional flow cytometric analysis will elucidate differential T cell and 
invariant NKT cell activation responses involved in the expression of peanut allergy in subjects 
prior to and after desensitization through detection of the following. 
 
a. Cytokines: IL-2, IL-4, IL-10, IFN G, IL-13, IL-12, IL-5, IL-17, CD152 
b. Transcription factors: GATA-3, T-bet, STAT-6, STAT-4 
c. Memory Cell Surface Markers: CCR-7, CD45RO 
d. Activation Surface Markers: CD40L, CD25, CD69, CD30, IL12RB2 
e. T regulatory markers: CD127, CD39, CD73, GARP, Foxp3 
 
A TH2 CD4+ T cell response and invariant NKT cell response, characterized by the intracellular 
expression of GATA3, IL-4 and IL-13 will characterize the responses in peanut allergic subjects 
prior to desensitization and, afterwards, peanut allergic patients will have a CD4+ T cell response 
with a higher t-bet, IL-5, IL-10, INF gamma, IL-17 and FOXP3 expression and an increased 
regulatory and memory T cell phenotype. 
 
The clarification of the roles of TH1, TH2, TH17, iNKT and T regulatory peanut specific antigen 
responses in peanut allergic disease before and after desensitization will help define immune 
mechanisms involved in the expression of allergic inflammation in vivo in peanut allergy. T cell 
epitopes will be determined through tetramer technology on saved samples, requiring HLA typing 
of all participants through buccal mucosal scraping analysis. Gene profiling will be performed on 
samples as well. Furthermore, basophil histamine release assays will also serve as an additional 
measure to discriminate between individuals who have developed tolerance and those that have 
not. This research plan is likely to provide a framework for further investigation of responses 
underlying the development of IgE compared to non-IgE mediated food allergic disease. 
 
 
SIGNIFICANCE: 
 
Th1/Th2/Treg response 
 
CD4 positive T cells differentiate into different T helper and inducible Tregulatory (Treg) cells 
upon stimulation of antigens. (27) In particular, TH2 cells participate in immunity against 
helminthic infections as well as being involved in allergic diseases through the production of 
cytokines such as IL-4, IL-5 and IL-13. (27)  TH1 cells activate macrophages through the 
production of cytokines such as IFN γ, as well as CD8 cells to enhance intracellular killing. (28) 
Tregs suppress inflammatory responses by the secretion of inhibitory cytokines such as IL-10 
and TGF-β (13).  iNKT cells are skewed towards production of IL-4 and IL-13 in food allergic 
chidlren compared to non-food allergic children. (29,30) It is thought that the skewing of the 
delicate balance between these subtypes of T cells toward TH2 leads to allergic disease. 
 
Currently, in the literature, there have been several studies showing an increase in cytokines and 
transcription factors associated with a TH2 phenotype with a suppression of the TH1 response in 
allergic disease.  It has been well established that atopic subjects often exhibit defective 
expression of T-bet, a transcription factor essential for TH1 development, whereas non-allergic 
subjects do not. (31)  Likewise, it has been shown that although patients with peanut allergy 

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show TH2 polarization by peanut-specific T cells, non-allergic children and children who have 
outgrown their allergy, show TH1 skewing to peanut antigens. (32) This was determined by 
measuring intracellular T cell production of IFN-y, TNF-a, IL-4, IL-5, and IL-13 to peanut 
antigen stimulation. This method has been extended to assess eosinophilic gastrointestinal 
disease (29), but has not been assessed with a polyfunctional flow cytometric method to assess 
multiple cytokines within one cell simultaneously. (32-34) 
 
In allergy and asthma models, there is evidence that Treg cells control disease in a manner that is 
dependent upon IL-10 (35) and some reports suggest IL-10 induction of TGF-β is important. (36) 
IL-10 is important in the regulation of T cell induced colitis. (37) IL-10 production by Treg cells 
has been shown to be essential for the maintenance or induction of tolerance in food allergy. 
While there remains some controversy and inconsistency in the literature, it has been reproduced 
multiple times in separate studies that in patients with atopic disease compared to those with 
healthy controls, there are often decreased numbers of FoxP3+ cells, a marker of T-regulatory 
cells. (38-42) 
 
Although there is strong evidence for a balance of T helper cell subtypes directing the immune 
response that leads to these allergic processes, there are very few studies in the literature that 
look at the specific intracellular production of cytokines in T helper cells upon antigenic 
stimulation of T cells.  Most studies look at serum cytokine production or T cell production in 
supernatants after stimulation (43-46), which may differ from what is produced intra-cellularly. 
In addition, no studies look at the combination of TH1, TH2, iNKT cell and Treg responses to 
peanut antigens before and after desensitization. Also, while some studies look at transcription 
factors or cytokines, few have looked at the combination of transcription factor and cytokine 
production, and no studies have evaluated the combination of memory cell production, activation 
markers, transcription factors, and cytokine production after peanut allergen stimulation. 
Decreasing these deficiencies in the literature is integral to understanding these disease processes 
and development of future therapeutic options. 
 
We propose to close these gaps by the following specific aims. We intend to use polyfunctional 
flow cytometry to establish the T cell response in patients with peanut allergy before and after 
desensitization. Polyfunctional flow cytometry allows us to look at multiple markers at the same 
time, which would allow us the luxury of evaluating the TH1, TH2, TH17, iNKT and Treg 
responses together.  We can also look at multiple factors including cytokine production, memory 
cell creation, transcription factors, as well as activation factors.  This would give us a broad 
scope of what the true responses of T and NKT cells are in patients with peanut allergy. 
 
INNOVATION 
 
Cytokine production of T lymphocytes has been performed in peanut allergic patients but this is 
typically performed through multiplex ELISA from supernatants of cultured cells. (43-46) 
Intracellular cytokine staining of T cells has been performed in peanut allergic patients (32, 46- 
47) but the relationship of production of T cell cytokines and transcription factors intracellularly 
in peanut allergy has not been studied. 

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In prior investigations of intracellular T cell responses in peanut allergic disease, the number of 
cytokines assessed was no more than four or five per cell. The cytokines assessed have included 
IFN-y, TNF-α, IL-4, IL-5, IL-10 and IL-17. Makedonas et al. (16) have established a model of 
assessment of T cell activation through a polyfunctional 14 color flow cytometry in virus specific 
CD8+ T cells. (16) Intracellular cell surface markers, cytokines and transcription factors were 
analyzed with this approach.  This comprehensive examination of T lymphocyte function has 
never been performed in the context of food allergic disease. We propose to evaluate peanut 
specific CD4+ T cell activation by polyfunctional analysis in distinct clinical phenotypes of 
peanut allergy. The ability to determine TH1, TH2,TH17 iNKT and T regulatory responses on a 
cellular level will give further insight into the mechanisms controlling the clinical expression of 
food allergy. 
 
 
6.8. 
Correlative studies: 
 
The peanut-specific immunoglobulin G and G4 tests and immune cell experiments in this study 
are designed for research, not for medical purposes. They are not useful for finding problems or 
diseases.  Even though the researchers are not looking at the subject’s peanut-specific 
immunoglobulin G and G4 tests to find or treat a medical problem, he or she will be told if they 
notice something unusual. The subject and his or her regular doctor can decide together whether 
to follow up with more tests or treatment.  Because the food-specific immunoglobulin G and G4 
tests and immune cell experiments done in this study are not for medical purposes, the research 
results will not be sent to the subject or to their regular doctor. 
 
 
The basophil histamine release assay, also known as the basophil activation test (BAT) will be 
performed on blood samples collected from subjects throughout the study.  The findings from 
BAT are designed for research and will not be sent to the subject or their regular doctor. 
 
6.9. 
Procedures for storing of extra or left over samples: 
 
Any extra serum will be stored in a freezer in the Allergy and Immunology laboratories at Texas 
Children's Hospital in Houston. 
The sample will be labeled with the subject’s unique identifier number. The subject’s name and 
personal information will not be included on the label. The link to the unique identifier number 
will be stored in a binder in Dr. Davis’s office in a locked cabinet in Houston. 
The samples will be accessible by Dr. Davis and other study personnel. 
If samples are used for reasons apart from those listed in this study (measuring food-specific IgE, 
IgG and IgG4, cellular immune studies) a study protocol will be submitted and an approval must 
be granted by the Institutional Review Board (IRB) of Baylor College of Medicine before the 
serum can be used. 
 
6.10. Criteria for Premature Termination of the Study (Stopping Rules): 

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Potential adverse reactions seen in subjects treated with peanut OIT and subjects undergoing 
DBPCFC include the following: skin manifestations such as pruritus, urticaria, or angioedema; 
respiratory symptoms such as wheezing, coughing, nasal congestion/rhinorrhea, cough and 
hoarseness; and gastrointestinal manifestations such as vomiting, diarrhea, or abdominal pain. 
Eosinophilic esophagitis, an allergic gastrointestinal disease, can also occur. Anaphylaxis is a 
potential risk involving any of the above symptoms plus hypotension and circulatory collapse. 
The study will be stopped and reviewed by the Principal Investigator and the IRB if: 
• 
Any death (grade 5) related to peanut OIT dosing 
• 
Greater than 2 anaphylactic reactions listed as a Grade 4 as defined by the World Allergy 
Organization grading scale for systemic reactions to immunotherapy related to peanut OIT 
dosing at any stage of the protocol. All patients will stay at their highest tolerated dose until the 
study re-opens. 
• 
Greater than 3 subjects that require greater than 1 injection of intramuscular epinephrine 
during oral dose escalation or maintenance of the peanut flour 
• 
Greater than 2 cases of new onset eosinophilic esophagitis 
The Principal Investigator and Co-Investigators are responsible for collecting and recording all 
clinical data.  As these results are collected, all toxicities and adverse events will be identified 
and reported to the principal investigator. The Principal Investigator will determine relationship 
of the event to the study intervention and decide course of action for the study participant. 
 
6.11. Participant Withdrawal Criteria: 
 
No subject initiating therapy in this trial will be replaced. The stopping rules for individual 
subjects are as follows: 
 Greater than or equal to four missed or ‘no-show’ appointments and four missed home 
doses, 
 Greater than 4 instances of not having or carrying an unexpired epinephrine injector to 
appointments 
 Anaphylactic reaction listed as a Grade 4 as defined by the World Allergy Organization 
grading scale for systemic reactions to immunotherapy related to peanut OIT dosing at 
any stage of the protocol. 
 Any participant is diagnosed with eosinophilic esophagitis 
 Any participant is diagnosed with moderate to severe asthma based on the NHLBI 
guidelines 
 Any participant needs treatment with greater than medium daily doses of inhaled 
corticosteroids, as defined by the NHLBI guidelines 
 Any participant has an accidental peanut ingestion with anaphylaxis during the time on 
oral desensitization 
 
 
Participants may be prematurely terminated from the study if: 

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 The participant elects to withdraw consent from all future study activities, including 
follow-up 
 The participant is “lost to follow-up” (i.e., no further follow-up is possible because 
attempts to reestablish contact with the participant have failed) 
 The participant dies 
 
 
6.12. Follow-up of Discontinued Participants 
 
Participants who prematurely discontinue treatment with study drug will remain in the study 
until normal termination. Subjects may receive the option of receiving a peanut equivalent if 
indicated. All willing subjects will be followed for the duration of the study, and continue blood 
draws for mechanistic studies while on a peanut restricted diet, and be monitored for accidental 
ingestions and safety parameters. 

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Procedure 
Screening 
(Visit 1) 
Entry Oral 
Food 
Challenge 
(Visit 2) 
Buildup 
Phase  
Visit 
#3-28 
(Weeks  
0-50) 
0 month of 
maintenance 
phase 
(Visit 29) 
0 Month 
DBPCFC 
(Visit 30) 
6 
months 
mainten
ance 
phase 
(Visit 31) 
12 
months 
mainten
ance 
phase 
(Visit 32) 
18 
months 
maintena
nce 
phase 
(Visit 33) 
24 
months 
mainten
ance 
phase 
(Visit 34) 
25 months 
maintenan
ce phase 
(Visit 35) 
End of 
Study 
Visit 
(Visit 36) 
Unscheduled 
visits 
Medical/Allergy 
Hx 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Spirometry or 
Peak Flow 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Physical Exam 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Diet Hx 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
Targeted Hx 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Review 
Home 
 
 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
FAQLQ/F
AIM 
 
 
 
 
 
 
 
 
 
 
X 
 
Endpoint 
titration 
 
X 
 
 
X1 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
 
 
Texas 
Children's 
Hospital in 
Houston OIT 
Administrati
on 
 
 
 
 
X 
 
 
X7 
 
 
 
 
 
 
X 
X 
OIT 
Maintenance 
 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
 
 
 
Entry 
Oral 
Food 
Challen
ge (1 
gram of 
peanut 
protein) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Oral food 
challenge 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 

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1 will be obtained after 24 week build-up 
2 will check only peanut -specific IgE at the screening visit. 
3 will be obtained at week 6, 12, 18, 24, 30, 36, 42, 48 of build-up phase only. 
4Beta HCG serum pregnancy test 
5 Urine pregnancy test 
6Maximum amount of blood drawn (4 mL/kg) 
7Peanut Equivalent Dose 
8Buccal mucosa will be performed only once after 6 months maintenance visit has been reached for HLA typing to allow for tetramer analysis
 
Procedure 
Screening 
(Visit 1) 
Entry Oral 
Food 
Challenge 
(Visit 2) 
Buildup 
Phase  
Visit  
#3-28 
(Weeks  
      0-50) 
0 month 
of 
maintena
nce 
phase 
(Visit 29) 
0 
Month 
DBPC
FC 
(Visit 30) 
6 months 
maintena
nce 
phase 
(Visit 31) 
12 
months 
maintena
nce 
phase 
    (Visit 32) 
18 months 
maintenanc
e phase 
   (Visit 33) 
24 months 
maintenan
ce phase 
     (Visit 34) 
25 months 
maintenan
ce phase 
    (Visit 35) 
End of 
Study 
Visit 
   (Visit 36) 
Unsche
duled 
Visit 
Blood 
draw for 
immune 
cell studies 
 
 
X 
 
X3 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
Buccal 
mucosal 
scraping 
for HLA
 
 
 
 
 
 
 
X8 
 
 
 
X8 
 
 
X8 
 
 
X8 
 
  
X8 
 
  
 
 
 
Pregnancy 
test 
 
X4 
 
 
 
X5 
 
X5 
 
X5 
 
X5 
 
 
 
Amount of 
blood to 
be drawn 
 
1-2 tsp 
 
4 – 6 tbs 6 
 
4 – 6 tbs 3,6  
 
4 – 6 
tbs 6 
 
4 – 6 tbs 
6 
 
4 – 6 tbs 
6 
 
4 – 6 tbs 6 
 
4 – 6 tbs 6 
 
4 – 6 tbs 6 
 
 
 
Time required 
per visit 
~3 hour 
~9 hours 
~3 hours 
~3 
hours 
~9 
hours 
~1 
hours 
~1 hours 
~1 hours 
~9 hours 
~9 hours 
~3 
hours 
~3 
hours 

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7. POTENTIAL RISKS AND DISCOMFORTS: 
 
Peanut oral immunotherapy may cause some, all or none of the side-effects listed below. 
 
The buildup and daily maintenance doses of OIT may cause allergic symptoms. The likelihood 
of a subject experiencing any allergic symptoms will be lessened by initiating dosing at 
extremely small amounts of the peanut protein. 
 
Symptoms often seen with therapy and during the food challenges: 
 
 
Likely (more than 20% of subjects) 
 Rare bursts of sneezing or nasal itching 
 Occasional sniffling 
 Mild congestion 
 Occasional scratching 
 Mild nausea or abdominal pain (e.g. no change in activity level) (~43% of 
subjects on initial escalation day) 
 Moderate nausea or abdominal pain (e.g. noticeable decrease in activity level) 
(~29% of subjects on initial escalation day) 
 1 episode of vomiting or diarrhea 
 Throat clearing 
 Occasional cough 
 Mild urticaria (less than 3 hives) 
 Mild rash (few areas of faint redness) 
Unlikely (2 – 20% of subjects) 
 Frequent sniffling 
 Hoarseness or a frequent dry cough 
 2 to 3 episodes of vomiting or diarrhea 
 Itching of more than 50% of the body 
 Skin redness covering more than 50% of the body 
 Hives covering more than 50% of the body 
 Continuous scratching for more than 2 minutes 
 Wheezing 
Serious but Rare (less than 2% of subjects) 
A potential risk associated with both the desensitization procedure and food challenge is the 
risk of a severe allergic reaction, called anaphylaxis, which may occur in <2% of patients. 
Symptoms of anaphylaxis may include those listed above (itchy rash, hives, facial swelling, 
wheezing, cough, shortness of breath, vomiting, diarrhea), and in severe cases low blood 
pressure, loss of consciousness, and, rarely, death.  Medication, personnel, and equipment 
are immediately available in the event of an anaphylactic reaction. 
The potential discomforts with the desensitization procedure or food challenge are no more 

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Subjects will be taught proper administration of the peanut protein and will be given specific 
instructions on the types of symptoms to look for in case the subject is having an adverse 
reaction.  Symptoms will be recorded daily on a home diary and reviewed every 2 weeks at each 
up-dosing visit. 
 
Subjects will be required to carry 2 epinephrine auto-injector devices at all times and must 
demonstrate to the investigators the correct use of the epinephrine auto-injector.   Failure to 
consistently carry an epinephrine auto-injector constitutes grounds for termination from the 
study.  If the subject does not have an epinephrine auto-injector on their person, their 
appointment will be rescheduled. 
 
Loss of Confidentiality: 
Any time information is collected; there is a potential risk for loss of confidentiality. Every 
effort will be made to keep the subject’s information confidential; however, this cannot be 
guaranteed. 
 
If parents or guardian asks, they will be told the results of a pregnancy test or that the subject is 
using birth control. 
 
Risks of Blood Drawing: 
Risks associated with drawing blood include minimal discomfort and/or bruising.  Infection, 
excess bleeding, clotting, and/or fainting also are possible, although unlikely. 
 
Subjects will have approximately 1-2 teaspoon of blood drawn at the screening visit, 4-6 
tablespoons of blood will be drawn at the food challenge visit and then 4 to 6 tablespoons of 
blood drawn approximately every 6 weeks during the first year and every 6 months during the 
second and third years for a total of approximately 14 times. The total amount of blood for the 
entire study will be 60–90 tablespoons. 
 
Risks of Allergy Skin Tests: 
The risk involved with skin testing includes discomfort from the needle prick, along with 
itching and swelling at the skin test site in positive responses. Less common side effects include 
severe allergic reactions. 
 
Financial Risks: 
Subjects will not have extra costs incurred because of the study apart from missed work 
secondary to study-related appointments.  Subjects will not be responsible for charges 
associated with allergy prick skin tests, blood tests (except for serum IgE), urine pregnancy 
tests, study dose increases, or food challenges. However, routine medical care for the subject’s 
condition will be charged to the subject. 
than when eating the suspected food in the past. Symptoms usually are short-lived (less 
than 2 hours). To minimize the risk of reaction, small amounts of the food suspected to 
cause a reaction will be given at the start of the desensitization procedure and food 
challenge. 

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Compensation for an injury resulting from participation in this research is not available from 
Baylor College of Medicine or Texas Children's Hospital in Houston. 
 
For Females of Reproductive Potential 
Being a part of this study while pregnant may expose the unborn child to significant risks, some 
of which may be currently unforeseeable. 
 
Other Risks 
There may possibly be other side effects that are unknown at this time. 
 
 
8. DATA MANAGEMENT ISSUES 
 
 
8.1. Sources of Research Material: 
 
8.1.1. 
Existing records: 
Previous CAP-FEIA serum IgE reports will be included in each subject’s record. 
Existing subject medical records will not otherwise be used unless records are needed 
to verify or clarify the severity of the original reaction to peanut ingestion. 
 
8.1.2. Data collected during research: 
 Consent and assent 
 Demographic information (age, sex, ethnicity) 
 History and Physical examination (including diet history, family history, past 
medical and past surgical history) 
 Allergy skin prick testing to peanut 
 Mechanistic blood draws 
 Serum Beta HCG and urine pregnancy test for all menstruating females. 
 Observed dosing adverse event log. 
 Concomitant medication administration while on study. 
 Spirometry and/or peak flow 
 Double-Blinded Placebo Controlled Food Challenge (DBPCFC) (for those 
with confirmed CAP-FEIA serum IgE > 7 and a negative pregnancy test). 
 
8.1.3. Home diaries: 
Symptom diaries will be recorded daily by participants. 
 
 
8.2. Data and Safety Monitoring Plan 
 
This study will be reviewed regularly by a Data and Safety Review Committee (DRC). 
The DRC will monitor the study for progress and enrollment, toxicities, adverse events, 
and soundness of data. The committee will consist of Drs. Lenora Noroski, Filiz 

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Seeborg, Robert Shulman and Christy Nance. All the members of the Data Safety 
Monitoring Board are affiliated with Baylor College of Medicine. 
 
 
8.3. Quality Assurance 
 
Quality Assurance (QA) Review will be conducted at least once shortly after initiation of 
participant recruitment, annually during the study (or more frequently if indicated), and at the 
end or closeout of the trial. The number of participants audited will be determined by 
available time and the complexity of the protocol. 
 
The audit will include a review of source documentation to evaluate compliance for: 
• 
Informed consent documents and procedures 
• 
Adherence to eligibility criteria 
• 
Protocol defined treatment 
• 
Required baseline, on study and follow-up protocol testing 
• 
IRB and other regulatory documents (submitted amendments, annual continuing review 
reports, SAEs) 
• 
Case Report Form submissions: timelines and accuracy 
 
Each QA review will be summarized and a final report will be sent to the PI within 30 days 
of the completion. The report will include a summary of findings, participant by participant 
case review, specific recommendations on any performance and/or shortcomings and request 
for corrective action, when necessary. 
 
 
9. MEASUREMENT OF EFFECT 
 
 
9.1. Response Review: 
 
The Data Safety Monitoring Committee will review the responses to the primary and 
secondary objectives every 6 months during the trial. 
 
 
9.2. Response Criteria: 
 
9.2.1. 
The primary objective will be measured by recording the daily symptoms 
experienced by the subjects and the number of subjects with no clinical symptoms during 
6 g peanut flour challenge at time 50 weeks compared to time 0 weeks. The change in 
tolerated dose will be assessed between baseline and one year. The proportion of 
patients who tolerate 6 g of peanut flour will be compared at baseline and at the one   
year point using McNemar’s test for matched pair data. The proportion of subjects will 
be estimated with exact binomial confidence intervals.  
 
9.2.2. 
For the first secondary objective, flow cytometric analysis of T, NKT cells, and 
basophils will be performed through the measurement of the percent of cells producing a 

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cytokine as well as measuring surface and intracellular markers expressed upon 
activation and the significance of changes from time 0 to 1 year will be assessed as 
described below by using a paired t-test of the log-transformed data. Baseline measures 
of cell activation will be summarized by means with standard deviation. Normality will 
be assessed by quantile-quantile plots, and non-normality will be addressed by data 
transformations. A general linear mixed model will be used to estimate the effect of the 
therapeutic procedure over time. The model will include a fixed effect for time 
(discrete), and the matrix of correlated error terms will assume a first-order 
autoregressive structure. Alternative correlation structures such as the unstructured and 
compound symmetry will be considered. Correlation structures will be assessed by 
Akaike’s Information Criteria. The likelihood ratio test will be used to test for overall 
significance of the model. P-values will be adjusted using the Holm’s step down 
Bonferonni correction for multiple comparisons. Activation responses that are significant 
at the 0.05 level after adjustment will be further assessed. Pairwise comparisons between 
discrete time points will be tested for significant differences, and p-values will be 
adjusted using the Bonferonni correction. Statistical significance of the adjusted p-values 
will be assessed at the 0.05 level. 
 
Spearman rank correlations will be estimated for all pairwise comparisons between 
activation responses. P-values for testing for significant correlations will be adjusted 
using Bonferonni’s correction for multiple comparisons. Partial correlation coefficients 
will also be estimated for all activation responses adjusting for subject-level effects 
across all time points. 
 
9.2.3. 
The second secondary objective will be assessed by recording the number of 
episodes of prior viral infection symptoms experienced after symptomatic daily peanut 
dosing. This number will be compared to the episodes of symptomatic daily peanut 
dosing with no prior viral infection symptoms. The proportion of subjects will be 
estimated with exact binomial confidence intervals. This analysis will also be used to 
determine the proportion of symptomatic daily doses with preceding symptoms of viral 
infection compared to non-viral associated symptomatic daily doses. 
9.2.4. 
The third secondary objective will be assessed by the comparison of amount of 
peanut protein tolerated at the 24 month food challenge to the 25 month food challenge 
using McNemar’s test for matched pair data. 
 
 
10. STATISTICAL CONSIDERATIONS 
 
 
10.1. Sample size considerations: 
 
Sample size was estimated to detect a statistically significant difference in the proportion of T 
cells producing interferon-gamma (IFN gamma),  at the 1 year time point compared with 
baseline using a paired t-test. A difference in proportions of 0.60 units (.2 at baseline and .8 at 1 
year) would be clinically important. Assuming a common SD=0.6 at each time point, correlation 
between repeated measures is 0.50 and alpha = 0.05, a sample size of 10 subjects would be 
required to detect this difference with 80% power. Assuming 50% attrition, this study will plan 
to enroll a total of 15 subjects. 

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Notes: 
 
 13 subjects for 90% power with alpha=0.01 
 16 subjects for 80% power with alpha=0.01 
 19 subjects for 90% power with alpha=0.01 
 
 
 
 
 
11. PROTECTION OF HUMAN SUBJECTS 
 
Potential benefits if the therapy is tolerated include: the potential decrease in the subject’s 
reactivity to peanuts after an accidental ingestion of peanut, altering the natural progression of 
peanut allergy, becoming clinically and immunologically tolerant to peanut, which is otherwise 
not likely to happen, and the ability to broaden their diet and lead a more normal life without the 
restrictions caused by having a potentially severe food allergy. This study will also help to 
expand the knowledge of food allergy in general and may lead to new management and 
therapeutic protocols for individuals with other food-allergies. 
 
All data will be kept on secure internal databases on the Texas Children's Hospital and Baylor 
College of Medicine servers. The files will be password protected and deleted at the earliest 
possible convenience. When feasible, all data will be stripped from identifiers to reduce the risk 
of patient identifiable information from being intercepted by unauthorized parties. Our research 
team knows and understands that it is our responsibility to protect patient records and personal 
information and will fully abide to HIPAA regulations. 
 
The subjects will not be financially responsible for any research-related clinic visits, procedures, 
or peanut oral immunotherapy. Standard of care clinic visits and laboratory and diagnostic tests, 
however, will have to be covered by the patient or patient’s insurance. 
 
Participation will be voluntary and will require informed consent by the patient or his/her 
legally authorized representative, parent, or guardian according to state regulations. The patient 

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and family will have to be fully aware of potential worsening of symptoms when even life- 
threatening conditions may emerge necessitating surgical and/or intensive care interventions. 
 
 
 
12. ADVERSE EVENTS 
 
 
12.1. Adverse Event (AE) or Medical Event: 
 
An adverse event is a new, undesirable medical event or occurrence or worsening of an 
existing condition (including an abnormal laboratory finding) in a subject that occurs 
during treatment and throughout the study, whether or not it is considered to be study 
related. This includes the following: 
 AEs not previously observed in the patient that emerge during the protocol-specified AE 
reporting period, including signs or symptoms associated with peanut allergy that were 
not present prior to the AE reporting period 
 Complications that occur as a result of protocol-mandated interventions (e.g., invasive 
procedures such as biopsies) 
 If applicable, AEs that occur prior to assignment of study treatment associated with 
medication washout, treatment run-in, or other protocol-mandated intervention 
 Preexisting medical conditions (other than the condition being studied) judged by the 
investigator to have worsened in severity or frequency or changed in character during the 
protocol-specified AE reporting period 
Potential adverse reactions seen in subjects treated with peanut OIT and subjects 
undergoing DBPCFC include the following: skin manifestations such as pruritus, urticaria, 
or angioedema; respiratory symptoms such as wheezing, coughing, nasal 
congestion/rhinorrhea, cough and hoarseness; and gastrointestinal manifestations such as 
vomiting, diarrhea, or abdominal pain.  Anaphylaxis is a potential risk involving any of the 
above symptoms plus hypotension and circulatory collapse. 
 
 
12.2. Serious Adverse Event: 
 
A serious adverse event is defined as any adverse therapy experience occurring at any dose 
that results in the following: 
 Death: A death occurring during the study, or which comes to the attention of the 
investigator during the protocol-defined follow-up after the completion of therapy 
whether or not considered treatment related, must be reported. 
 Life-threatening: Any adverse therapy experience that places the subject or subjects, 
in the view of the investigator, at immediate risk of death from the reaction as it 

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occurred (i.e., it does not include a reaction that had it occurred in a more serious 
form, might have caused death). 
 In-patient hospitalizations or prolongation of existing hospitalization. 
 Persistent or significant disability or incapacity. 
 Congenital anomaly/birth defect. 
 An event that required intervention to prevent permanent impairment or damage. 
All AEs that do not meet any of the criteria for serious should be regarded as non- 
serious AEs. 
Each recorded AE or SAE will be described by its duration (i.e., start and end 
dates), severity, regulatory seriousness criteria if applicable, suspected relationship 
to the investigational product (see below), and actions taken. 
 
 
12.3. Expected adverse event and unexpected adverse event: 
 
Expected adverse events are those that have been previously identified as resulting from 
administration of the agent.  For purposes of this study, an adverse event is considered 
expected when it is included in the protocol and informed consent document as a 
potential risk. 
 
An adverse event is considered unexpected when it varies in nature, intensity, or 
frequency from information provided in the current adverse event list in the protocol and 
informed consent document as a potential risk. 
 
 
12.4. Toxicity Grading 
 
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of 
an AE (as in mild, moderate, or severe pain); the event itself may be of relatively minor 
medical significance (such as severe headache). “Serious” is a regulatory definition and 
is based on patient or event outcome or action criteria usually associated with events that 
pose a threat to a patient’s life or vital functions. Seriousness (not severity) serves as the 
guide for defining regulatory reporting obligations. 
 
Toxicity grades are assigned to indicate the severity of adverse experiences and 
toxicities using The World Allergy Organization (WAO) as displayed in Table 8. The 
World Allergy Organization (WAO) (44) has been reviewed specifically for this 
protocol and is otherwise appropriate for this study population. The purpose of using 
the WAO system is to provide standard language to describe toxicities and to facilitate 
tabulation and analysis of the data and assessment of the clinical significance of 
treatment-related toxicities. The NCI-CTCAE grading system will be used for all 
adverse events except for allergic reactions, for which the WHO criteria will be used. 

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Table 8.  Grading System for Adverse Event Allergic Reactions 
 
Current grading systems for allergic reactions used by World Allergy Organization for allergic 
reactions to immunotherapy as displayed below. (17) 
 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Life threatening 
Grade 5 
Death 
Symptom(s)/ sign(s) of 
one organ system 
present 
Cutaneous 
Generalized pruritus, 
urticaria, flushing or 
sensation of heat or 
warmth 
or 
Angioedema (not 
laryngeal, tongue or 
uvular) 
or 
Upper respiratory 
Rhinitis (e.g., sneezing, 
rhinorrhea, nasal 
pruritus 
and/or nasal congestion) 
or 
Throat-clearing (itchy 
throat) 
or 
Cough perceived to 
come from the upper 
airway, not 
the lung, larynx, or 
trachea 
or 
Symptom(s)/ sign(s) 
of more than one 
organ system present 
or 
Lower respiratory 
Asthma: cough, 
wheezing, 
shortness of breath 
(e.g., less than 
40% PEF or FEV1 
drop, responding 
to an inhaled 
bronchodilator) 
or 
Gastrointestinal 
Abdominal cramps, 
vomiting, or 
diarrhea 
or 
Other 
Uterine cramps 
Lower 
respiratory 
Asthma (e.g., 
40% PEF or 
FEV1 drop, 
NOT responding 
to an inhaled 
bronchodilator) 
or 
Upper 
respiratory 
Laryngeal, uvula 
or tongue edema 
with 
or without stridor 
Lower or Upper 
respiratory 
Respiratory failure 
with or without loss 
of consciousness 
or 
Cardiovascular 
Hypotension with 
or without loss of 
consciousness 
Death 

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Conjunctival 
Conjunctival erythema, 
pruritus or tearing 
Other 
Nausea, metallic taste, 
or headache 
 
Relationship to Procedure Definitions 
Associated: There is a reasonable possibility that the adverse event may have been 
caused by the test product and/or procedure.  This definition applies to those adverse 
events that are considered definitely, probably or possibly related to the procedure. 
 
1. 
Definitely related: An adverse event that follows a temporal sequence from 
administration of the test product and/or procedure; follows a known response 
pattern to the test article and/or procedure; and, when appropriate to the 
protocol, is confirmed by improvement after stopping the test product (positive 
re-challenge: and by reappearance of the reaction after repeat exposure 
[positive re-challenge]); and cannot be reasonably explained by known 
characteristics of the subject’s clinical state or by other therapies. 
 
2. 
Probably related: An adverse event that follows a reasonable temporal 
sequence from administration of the test product and/or procedure; follows a 
known response pattern to the test product and/or procedure, is confirmed by 
improvement after re-challenge; and cannot be reasonably explained by the 
known characteristics of the participant’s clinical state or other therapies. 
 
3. 
Possibly related: An adverse event that follows a reasonable temporal; 
sequence from administration of the test product and/or procedure and follows 
a known response pattern to the test product and/or procedure, but could have 
been produced by the participant’s clinical state or by other therapies. 
 
Not associated: An adverse event for which sufficient information exists to indicate that 
the etiology is not related to the test product and/or therapy. 
 
Unrelated: An adverse event that does not follow a reasonable temporal sequence after 
administration of the test product and/or procedure and most likely is explained by the 
participant’s clinical disease state or by other therapies.  In addition, a negative re- 
challenge to the test article and/or procedure would support an unrelated relationship. 

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12.5. Adverse Event Reporting 
 
All adverse events, regardless of perceived relationship to study treatment, will be 
reported and recorded on the appropriate Case Report Forms (CFR Title 21, 312.32). 
New AEs and SAEs that are ongoing at the end of the study will be followed for 30 days 
from the patient’s receipt of the last dose of protocol therapy, unless they have resolved 
earlier.  SAEs and treatment related AEs ongoing at the end of study will be followed 
until resolution. 
 
The AE description will include the nature of the experience, the date of onset, the 
resolution date, the severity of each sign or symptom reported using grade 1 to 5, the 
seriousness of the event, the potential relationship to study treatment, the course of 
action taken, and the outcome of the experience. 
 
Serious adverse events are to be reported to the institutional review board (IRB) 
according to each board’s reporting requirements and required time frame. 
 
The Principal Investigator will be responsible for reporting all adverse events to the 
FDA as per their reporting requirements and time frame. 
 
 
 
12.6. Safety Reporting Requirements for IND Holders 
 
Additional reporting requirements for the FDA in accordance with the guidance set 
forth in 21 CFR 212.32 are required. Sponsor-investigators of studies conducted 
under an IND will comply with the safety reporting requirements outlined below. 
 
12.6.1. Expedited IND Safety Reports: 
 
Seven calendar-day telephone or fax report: The Sponsor-Investigator is required to 
notify the FDA of any fatal or life-threatening adverse event that is unexpected and 
assessed by the investigator to be possibly related to the use of peanut OIT.  An 
unexpected adverse event is one that is not already described in the consent form. 
Such reports are to be telephoned or faxed to the FDA within 7 calendar days of first 
learning of the event.  Each telephone call or fax transmission (see fax number below) 
should be directed to the FDA new drug review division in the Center for Drug 
Evaluation and Research or in the product review division for the Center for Biologics 
Evaluation and Research, whichever is responsible for the review of the IND. 
 
12.6.2. Fifteen calendar-day written report: 
 
The Sponsor-Investigator is also required to notify the FDA and all participating 
investigators, in a written IND Safety Report, of any serious, unexpected AE that is 

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considered possibly related to the use of peanut OIT. 
 
12.6.3. Written IND Safety Reports: 
 
Will include an Analysis of Similar Events in accordance with regulation 21 CFR 
312.32.  All safety reports previously filed with the IND concerning similar events 
should be analyzed.  The new report should contain comments on the significance of 
the new event in light of the previous, similar reports. 
 
Written IND safety reports with Analysis of Similar Events are to be submitted to the 
FDA within 15 calendar days of first learning of the event. The FDA prefers these 
reports on a MedWatch 3500a Form but alternative formats are acceptable (e.g. 
summary letter). MedWatch Forms along with submission instructions can be found 
at the following FDA website: 
http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/default.htm. 
 
FDA fax number for IND Safety Reports:  1 (800) FDA - 0178 
 
12.6.4. IND Annual Reports 
 
In accordance with the regulation 21 CFR 312.32, the Sponsor-Investigator shall 
within 60 days of the anniversary date that the IND went into effect submit a brief 
report of the progress of the investigation.  Please refer to Code of Federal 
Regulations, 21 CFR 312.32 for a list of the elements required for the annual report. 

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13. REFERENCES 
 
1. 
Sampson H and Scanlon S. Natural history of food hypersensitivity in children with 
atopic dermatitis. J Pediatr. 1989;115(1):23-7. 
2. 
Kulis M, Burks AW. Oral immunotherapy for food allergy: Clinical and preclinical 
studies. Adv. Drug Deliv. Rev. (2012), http://dx.doi.org/10.1016/j.addr.2012.10.004. 
3. 
Skolnick HS C-WM, Koerner CB, Sampson HA, Burks W, Wood RA. The natural 
history of peanut allergy. J Allergy Clin Immunol. 2001;107:367-74. 
4. 
Ross MP FM, Street D, Klontz K, Schroeder T, Luccioli S. Analysis of food-allergic and 
anaphylactic events in the National Electronic Injury Surveillance System. J Allergy Clin 
Immunol. 2008;121:166-71. 
5. 
Sampson H, Mendelson L and Rosen J. Fatal and near-fatal anaphylactic reactions to 
food in children and adolescents. N Engl J Med. 1992;327:380-4. 
6. 
Lee J and Greenes D. Biphasic anaphylactic reactions in pediatrics. Pediatrics. 2000; 
10:762-6. 
7. 
Oppenheimer JJ et al. Treatment of peanut allergy with rush immunotherapy. J Allergy 
Clin Immunol. 1992;90:256-62. 
8. 
Nelson HS, et al. Treatment of anaphylactic sensitivity to peanuts by immunotherapy 
with injections of aqueous peanut extract.  J Allergy Clin Immunol. 1997; 99(6 Pt1):744- 
51. 
9. 
Hofmann AM, Scurlock AM, Jones SM, Palmer KP, Lokhnygina Y, Steele PH, 
Kamilaris J, Burks AW. Safety of a peanut oral immunotherapy protocol in children with 
peanut allergy. J Allergy Clin Immunol. 2009;124:286–291 [291 e281–86]. 
10. 
Varshney P, Jones SM, Pons L, Kulis M, Steele P, Kemper AR, Scurlock AM, Perry TT, 
Burks AW. Peanut oral immunotherapy (OIT) induces immunologic changes supporting 
the development of tolerance. J Allergy Clin Immunol. 2010;125:AB59. 
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14. APPENDICES 
Appendix I: 
A. Home Diary: Tolerance of Daily OIT Dose 
 
Subject ID:   
 Dose: 
mg 
Allergy:   
 
 
Date 
Time 
Dose taken 
(Yes or No) 
Amount Flour 
mixed with 
(tbsp. or ml) 
Type of food 
peanut flour is 
mixed with? 
Accidental 
ingestion (Yes 
or No) 
If peanut 
equivalent 
taken, how 
much of what 
equivalent? 
Viral Illness? 
(Yes or No) 
Premedicate? 
(Yes or No) 
 
Describe Symptoms RELATED TO DOSE (within 2 hrs) and enter the appropriate number in box 
0 = None 
1 = Mild 
2 = Moderate 
3 = Severe 
 
Date 
Time of 
reaction 
Skin 
Upper 
Respiratory 
Chest 
Abdomen 

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Other 
Medication 
given? 
(describe) 
 
 
Comments (please elaborate above; also note symptoms that were not likely related to dose): 
 
 
 
 
 
 
 
 
 
 

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B. Peanut Equivalent Home Diary: Tolerance of Daily OIT Dose 
 
Unique Identifier:   
 Dose: 
mg 
Allergy:   
 
 
Date: 
Time: 
Dose taken 
(Yes or No) 
Quantity of 
Peanut 
Equivalent 
Peanut 
Equivalent 
Food 
Type of food 
dose is given 
with, if 
applicable. 
Accidental 
ingestion (Yes 
or No) 
Viral Illness 
(Yes or No) 
Premedicate? 
(Yes or No) 
Describe Symptoms RELATED TO DOSE (within 2 hrs) and enter the appropriate number in box 
0 = None 
1 = Mild 
2 = Moderate 
3 = Severe 
Date: 
Time of 
reaction: 
Skin 
Upper 
Respiratory 
Chest 
Abdomen 
Other 

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Comments (please elaborate above; also note symptoms that were not likely related to dose): 
 
 
 
 
 
 
Medication 
given? 
(describe) 

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Appendix II: Symptom Scoring Sheet for Desensitization and Dosage Escalations 
 
I. 
Skin: 
A. Red rash - 
% area involved 
B. Rash 
0 Absent 
1 Mild – few areas of redness 
2 Moderate – areas of redness, flat and raised rash 
3 Severe – large areas of redness (>50%), large amount of raised rash on the body 
(>25%) 
C. Itchiness 
0 Absent 
1 Mild – occasional scratching 
2 Moderate – scratching continuous for more than 2 minutes 
3 Severe – continuous scratching all over 
D. Hives/Swelling 
0 Absent 
1 Mild – less than 3 hives 
2 Moderate – greater than 3 but less than 10 hives 
3 Severe – Body covered in hives 
 
II. 
Upper Respiratory: 
A. Sneezing/Itching 
0 Absent 
1 Mild – rare bursts of sneezing, mouth itching 
2 Moderate – less than 10 bursts of sneezing, sometimes rubbing of nose and/or 
eyes, mouth itching lasting longer than 10 min. 
3 Severe – continuous rubbing of nose and/or eyes, swelling around the eyes 
and/or sneezing often, swelling in or around the mouth 
B. Stuffy nose 
0 Absent 
1 Mild – small amount of trouble breathing through the nose 
2 Moderate – nose feels stuffy; breathes through mouth most of the time 
3 Severe – nose runs freely despite sniffling and tissues 
C. Runny nose 
0 Absent 
1 Mild – sniffling sometimes 
2 Moderate – sniffling often and need tissues 
3 Severe – nose runs freely despite sniffling and tissues 
D. Throat symptoms 
0 Absent 
1 Mild – throat clearing, cough 
2 Moderate – hoarseness, frequent dry cough 
3 Severe – Breathing causes loud, squeaky sounds 

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III. 
Chest: 
A. Wheezing 
0 Absent 
1 Mild – wheezing only heard when examined by physician 
2 Moderate wheezing from breathing in and out 
3 Severe – shortness of breath, use of chest muscles to breath, and wheezing 
 
IV. 
Abdomen: 
A. Subjective complaints 
0 Absent 
1 Mild – complaints of nausea or abdominal pain, no change of activity 
2 Moderate – frequent complaints of nausea or pain, decreased activity 
3 Severe – patient in bed; crying or notably distressed 
B. Objective complaints 
0 Absent 
1 Mild – 1 episode of emesis or diarrhea 
2 Moderate – 2 to 3 episodes of emesis or diarrhea or 1 of each 
3 Severe- more than 3 episodes of emesis or diarrhea or greater than 1 of each 
 
 
Algorithm for Dose Adjustment Based on Symptoms: 
 
A. For a Grade 1 reaction, the daily dose will be continued until the next visit. If a subsequent 
Grade 1 or greater reaction occurs, the participant will hold future doses and return to the 
clinic within 48 hours and be challenged to the previous tolerated dose. 
B. For a Grade 2 and 3 reaction, the participant will hold all future doses and return to the clinic 
within 48 hours to be challenged to the previous tolerated dose. If a Grade 3 reaction occurs 
greater than 2 times, the participant’s dose will remain at the highest tolerated dose and will 
enter the maintenance phase of the study. 
C. Grade 4 reaction will cause discontinuation of the study for that patient and the patient will 
be given the option to be converted to a peanut equivalent dose. 

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Appendix III: Instructions for Daily Home Doses 
 
Subject ID:    
 
Date:          /           /                   
 
 
Important: We require that you please carry with you 2 epinephrine auto-injector devices at all 
times and must demonstrate to the investigators the correct use of the epinephrine auto-injector. 
Failure to consistently carry an epinephrine auto-injector constitutes grounds for termination 
from the study.  If you do not have an epinephrine auto-injector on your person, your 
appointment(s) will be rescheduled. 
 
 Take one dose per day, preferably at the same time every day. Prior to taking the dose, 
you must eat a snack high in carbohydrate and fat (example: bagel, chips) then eat the 
peanut flour mixed in a small amount of liquid (example: less than 1 tablespoon (15 ml) 
of water, apple juice etc.) or mixed into another food (example: less than one half of a 
cup (8 tablespoons) of apple sauce, ice cream). Liquid or semi-solid foods can be mixed 
with the dose to facilitate consumption. 
 
After eating the flour, your child must be with a supervising adult for the next 2 hours so 
they can monitor for any possible reaction. Your child cannot go to school, go to bed, or 
take hot showers within 2 hours of eating the peanut flour. No strenuous physical activity 
during the observation period. 
 
 Travel 
o No international traveling is allowed 
o Domestic Traveling within the continental U.S. 
 Take dose at the same time as place of origin (i.e. dose time in Houston 
4pm, then take the dose at 4pm final destination) 
o No traveling on cruise ships 
 
 Please ensure that the vehicle food that the peanut flour is mixed with is not food that 
your child is allergic to. 
 
 Record any symptoms occurring within 2 hours of taking the daily dose. 
 
 
Symptoms to look for: 
Mild Symptoms 
(itching, mild flushing, sneezing, nasal congestion, eye itching, swelling of lips, 
hives/swelling in one or two areas of the body, nausea) 
Moderate to Severe Symptoms 
(hives/swelling all over the body, shortness of breath, cough, chest tightness, 
vomiting, abdominal pain, feeling of tightness around the throat, feeling faint, skin 

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 Please use the Allergic Reaction Treatment Plan as a guide during an allergic reaction. 
 
 Call and inform the research team of any reaction (even mild cases) and make an 
appointment to see the research team for the following day. 
 
 Please call 9-1-1 for severe reactions (example: confusion, loss of consciousness/non- 
responsive, collapse, incontinence, bluish skin, feeling faint). 
 
 
 
If a daily dose is missed: 
• Up to 2 days, continue doses as scheduled. 
• 3-4 days after missed dose; repeat previous doses but this dose will be given at Texas 
Children’s Hospital. 
• More than 4 days after missed dose, you/your child will return to Texas Children’s 
Hospital for a graded challenge. 
 
 Please store peanut flour doses in refrigerator with the container lid tightly closed. 
turning blue, and breathing with loud, squeaky sounds) 

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APPENDIX IV: 
 
Subject ID:    
 
Date:          /           /                   
How to Use EpiPen Auto-Injector Step-by-Step instructions 
(www.epipen.com) 
 
 
 
 
 
 
Source:      http://kidshealth.schn.health.nsw.gov.au/fact-sheets/epipen-use 

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1. Prepare the EpiPen or EpiPen Jr Auto-Injector for Injection 
o Remove the auto-injector from the clear carrier tube. Flip open the yellow cap of 
your EpiPen or the green cap of your EpiPen Jr Auto-Injector carrier tube. Tip 
and slide the auto-injector out of the carrier tube. 
o Grasp the auto-injector in your fist with the orange tip pointing downward. 
o With your other hand, remove the blue safety release by pulling straight up 
without bending or twisting it. 
Note: The needle comes out of the orange tip. 
o Never put your thumb, fingers or hand over the orange tip. 
 
 
2. Administer the EpiPen or EpiPen Jr Auto-Injector 
 
Hold the auto-injector with orange tip near the outer thigh. Swing and firmly push the 
orange tip against the outer thigh until it “clicks”. Keep the auto-injector firmly pushed 
against the thigh at a 90° angle (perpendicular) to the thigh. Hold firmly against the thigh 
for approximately 10 seconds to deliver the drug. The injection is now complete. 
 
3. Finalize the Injection Process 
 
Remove the auto-injector from the thigh. The orange tip will extend to cover the needle. 
Massage the injection area for 10 seconds. Get emergency medical help right away. You 
may need further medical attention. You may need a second EpiPen or EpiPen Jr Auto- 
Injector should symptoms persist or recur. 
 
Note: Take your used auto-injector with you when you go to see the health care provider. 
 
o Tell the health care provider that you have received an injection of epinephrine. 
Show the health care provider where you received the injection. 
o Give your used EpiPen or EpiPen Jr Auto-Injector to a health care provider for 
inspection and proper disposal. 
o Ask for a refill, if needed. 
o The used auto-injector with extended needle cover will not fit in the carrier tube. 

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APPENDIX V: 
Subject ID:    
 
 
 
Appendix V: 
 
Date:          /           /                   
 
EpiPen Auto-Injector Demonstration Check-Off 
 
Subject ID:    
 
Date:          /           /                   
Investigator: Please initial next to each procedure as they are properly demonstrated. 
 
Date 
Investigator 
Initial 
Procedures 
Correctly prepared the EpiPen or EpiPen Jr Auto-Injector for 
injection by: 
 removing the auto-injector from the clear carrier tube 
 removing the blue safety release by pulling straight up 
without bending or twisting it 
Correctly demonstrated proper administration of EpiPen or EpiPen 
Jr Auto-Injector by: 
 holding the auto-injector with orange tip near the outer 
thigh 
 firmly pushing the orange tip against the outer thigh until it 
“clicks” 
 kept the auto-injector firmly pushed against the thigh at a 
90° angle (perpendicular) to the thigh. 
 firmly held the auto-injector against the thigh for 
approximately 10 seconds to complete drug delivery 
Correctly finalize the injection process by: 
 removing the auto-injector from the thigh 
 massaging the injection area for 10 seconds 
 verbalized that they will call 9-1-1 immediately after for 
further medical attention 

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Caregiver Signature: 
Date:      __ /           /                   
 
Investigator Signature: _ 
Date:           /           /                   
 
 
 
 
Appendix VI: Peanut Oral Immunotherapy – Safety Checklist 
 
 
Subject ID:    
 
Date:          /           /                   
 
Please initial each line and sign/date at the bottom. 
 
  
I acknowledge that Caregiver understands the safety risks and implications of this 
study. 
 
  
 Caregiver received training and understand how to use an Epinephrine injector. 
 
  
 Caregiver received training and understands the signs and symptoms of an allergic 
reaction. 
 
  
 Caregiver received training and understands when to give Benadryl, when to use an 
Epinephrine injector, and when to call 9-1-1. 
 
  
 Caregiver understands the need to have their unexpired Epinephrine injector with 
them at all times. 
 
  
 Caregiver/ understands that if Epinephrine injector is not with them during a research 
related appointment, then that appointment will be canceled and rescheduled. 
 
  
 Caregiver understands that they will need to come to Texas Children’s Hospital every 
two weeks for the first year of the study, then every 6 months for the last two years of the study 
to receive their daily peanut doses. 
 
  
 Caregiver understands that they must notify the research team of any allergic 
reactions, even mild cases, on the day the reaction occurs. 
 
  
 Caregiver understands that they must call 9-1-1 for severe reactions and to obtain 
further medication attention. 
 
  
 Caregiver understands that they will need to come to Texas Children’s Hospital the 
next day if a reaction occurs at home. 

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 Caregiver understands that his/her child will need supervision 2 hours after taking 
their daily peanut dose at home. 
 
  
 Caregiver understands that his/her child cannot go to school within 2 hours of eating 
the peanut flour and cannot go to bed within 2 hours of eating the peanut flour. 
 
  
 Caregiver received a contact list of phone and pager numbers from research team and 
I know who to call if my child experiences an allergic reaction. 
 
  
Caregiver understand that the peanut flour needs to be stored in a refrigerator with the 
container lids tightly closed. 
 
  
 Caregiver understand that if his/her child misses 3-4 doses of peanut flour, they will 
have to come to Texas Children’s Hospital to receive their next scheduled dose. 
 
 
Investigator or designee Signature:   
 
 
Date:          /          /                   

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Subject ID:   
 
Appendix VII  
 
Date:          /           /                   
 
Peanut Equivalent Dosing Guide 
 
Warning: It is your responsibility to ensure the product is safe for your child to eat. 
 
 ALWAYS read labels on all foods 
 Ingredients and protein amount can change without warning at any time 
 These products may contain allergens and may not be safe for everyone 
 M&M’s and Reese’s products contain milk and may contain tree nuts 
 Be cautious about consuming candies manufactured outside the US 
 Call the manufacturing company if there are any doubts about the product containing 
other allergens 
 
 
 
 
Peanut Product 
Peanut Protein (gram) 
/serving 
Maintenance 
Dose 
(3900mg peanut 
protein) 
Alternative 
Dose 
(if maintaining 
below 3900mg) 
Creamy Peanut Butter 
*Peter Pan or Reese’s 
Creamy Peanut Butter* 
8 grams=2 Tablespoons 
1 Tablespoon 
1300 mg =1 
teaspoon 
325mg=0.25 
teaspoon 
JIF Peanut Powder 
8 grams=3 Tablespoons 
1.5 Tablespoons 
PB2 Powdered Peanut 
Butter (Bell Plantation) 
5 grams=2 Tablespoons 
1.5 Tablespoons 
1300 mg= 1.5 
teaspoon 
300 mg = 3/8ths 
of a teaspoon 
Dry Roasted Peanuts 
0.175 grams=1 peanut 
22 peanuts 
1300 mg = 7 
and ½ peanuts 

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350 mg = 2 
peanuts 
Peanut M&M’s 
0.15 grams=1 piece 
26 pieces 
1300 mg = 8 
and 2/3 pieces 
300 mg=2 
pieces 
Reese’s Pieces Candy 
0.078 grams=1 piece 
50 pieces 
1300 mg = 16 
and 2/3 pieces 
312 mg = 4 
pieces 
Reese’s Peanut Butter Cups 
Miniatures 
0.8 grams=1 miniature cup ̴5 miniature cups 
1300 mg = 1 
and 5/8th cups 
300 mg = 3/8th 
cup 
Other approved alternative: 
 
1. The peanut equivalent dose may vary depending on the maintenance dose. The table is 
based on a maintenance dose of 3900mg. 
 
2. You are able to choose any of the above foods to use for daily dosing. 
 
3. Ensure the peanut protein amount is the same prior to purchasing product. 
 
4. You should continue to follow the “Instructions for Daily Home Doses” as used for 
peanut flour dosing. 
 
 
Parent Signature: 
Date:     __ /          /                   
 
Investigator Signature: 
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Appendix VIII 
Peanut Equivalent Instructions for Daily Home Doses 
 
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Important: We require that you please carry with you 2 epinephrine auto-injector devices 
at all times and must demonstrate to the investigators the correct use of the epinephrine 
auto-injector.   Failure to consistently carry an epinephrine auto-injector constitutes 
grounds for termination from the study.  If you do not have an epinephrine auto-injector 
on your person, your appointment(s) will be rescheduled. 
 
 Take one dose per day, preferably at the same time every day. Prior to taking the dose, 
you must eat a snack high in carbohydrate and fat (example: bagel, chips) then eat the 
peanut equivalent based on the “Peanut Equivalent Dosing Guide”. 
 
 After eating the peanut equivalent, your child must be with a supervising adult for the 
next 1-2 hours (depending on provider’s instructions) so they can monitor for any 
possible reaction. Your child cannot go to school and cannot go to bed within the 
observation period. The provider may have the option of decreasing the observation 
period to 1 hour after 30 days of tolerating the peanut equivalent. Your child may eat and 
go to school after 1 hour. Your child should continue to avoid physical activity, hot 
showers, and going to bed within 2 hours of taking the dose. 
 
 Travel 
o International Traveling 
 May consider international traveling once the subject is stable on 
maintenance for 6 months 
 Try to keep the dosing time period the same as in the USA. Keep the 
dosing time the same as your place of origin (i.e. dose time in the USA 
4pm, then take the dose at 4pm final destination time). Up to 48 hours of 
dose could be missed 
 No dose should be taken during travel on the plane. Dosing may resume 
once you arrive at your final destination 
o Domestic Traveling within the continental U.S. 
 Take dose at the same time as place of origin (i.e. dose time in Houston 
4pm, then take the dose at 4pm final destination) 
o No traveling on cruise ships 

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 Please ensure that the peanut equivalent food is not a food that your child is allergic to. 
Also, be sure to read the label on the food. 
 
 Fill out symptom diary every day and record any symptoms occurring within the 
observation period of taking the daily dose. 
 
 
Symptoms to look for: 
Mild Symptoms 
(itching, mild flushing, sneezing, nasal congestion, eye itching, swelling of 
lips, hives/swelling in one or two areas of the body, nausea) 
Moderate to Severe Symptoms 
(hives/swelling all over the body, shortness of breath, cough, chest tightness, 
vomiting, abdominal pain, feeling of tightness around the throat, feeling 
faint, skin turning blue, and breathing with loud, squeaky sounds) 
 Please use the Allergic Reaction Treatment Plan as a guide during an allergic reaction. 
 
 Call and inform the research team of any reaction (even mild cases) and make an 
appointment to see the research team for the following day. 
 
 Please call 9-1-1 for severe reactions (example: confusion, loss of consciousness/non- 
responsive, collapse, incontinence, bluish skin, feeling faint). 
 
 
 
If a daily dose is missed: 
• Up to 2 days, continue doses as scheduled. 
• 3-4 days after missed dose; repeat previous doses but this dose will be 
given at Texas Children’s Hospital. 
• More than 4 days after missed dose, you/your child will return to Texas 
Children’s Hospital for a desensitization challenge procedure. 
 
Parent Signature: 
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Investigator Signature: 
Date:           /           /