Open Label Peanut Oral Immunotherapy in Children: IMPACT Follow Up Study
Phase: PHASE2
Conditions: Treatment Efficacy
Sponsor: Johns Hopkins University

 
  
JHMIRB eFormA  01  
Version 3 Dated:   06/2007  
  
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Open Label Peanut Oral Immunotherapy in 
Children: IMPACT Follow Up Study 
 
 
 
 
 
 
NCT03345160 
 
 
 
 
 
 
 
June 19, 2020 
 
 
 
 
 
 
 
 
 
  

Date: June 19, 2020  
Principal Investigator: Robert Wood  
Application Number: IRB00150453  
  
  
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JHM IRB - eForm A – Protocol  
  
  
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Open Label Peanut Oral Immunotherapy in Children: IMPACT Follow Up 
Study (IND #17784)  
  
1.  
Abstract  
  
This application is being submitted as a follow-up to Protocol NA_00077852 “Oral  
Immunotherapy for Induction of Tolerance in Peanut Allergic Children.”  The “IMPACT” protocol 
was a double-blind, placebo-controlled study of peanut oral immunotherapy in children 12-48 
months of age.  As part of the IMPACT protocol, all participants who received placebo treatment 
were promised the opportunity to receive open label treatment at the conclusion of the 
doubleblind phase and initial follow-up.  At the time of submitting  IMPACT, we did not specify 
any detailed protocol for the open label crossover treatment, as this is an evolving field, but we 
are now ready to offer this open label treatment as promised.  
  
There are no specific hypotheses to be tested.  The main research questions will focus on the 
safety and efficacy of the treatment.  
  
   
2.  
Objectives  
  
1. The primary objectives of this protocol is to provide open label peanut oral 
immunotherapy (OIT) for those subjects who received placebo treatment in the 
doubleblind phase of the above noted study and to assess safety, as measured by the 
incidence of adverse events and the proportion of subjects who discontinue treatment 
due to adverse events.  
  
Secondary objective will include:  
2. Efficacy of the treatment, as defined by an end of treatment oral peanut challenge.  
  
3.  
Background   
  
Anaphylaxis is a severe, potentially fatal, systemic allergic reaction that occurs suddenly after 
contact with an allergy-causing substance1. Peanut allergy affects 1-2% of US children and is 
associated with a high risk of life-threatening anaphylaxis. 2,3 Even more concerning, peanut is 
the allergen most commonly associated with death and near-death following food-induced 
anaphylaxis and is frequently encountered in common food products. Peanut allergy also 
persists into adulthood in the majority of affected individuals, with less than 25% of 
peanutallergic children naturally developing tolerance.    
  

Date: June 19, 2020  
Principal Investigator: Robert Wood  
Application Number: IRB00150453  
  
  
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Currently, treatment for peanut allergy is limited to dietary avoidance and ready access to 
selfinjectable epinephrine.  However, immunotherapy for food allergy has been evaluated 
extensively over the last decade with studies focusing on oral, sublingual and epicutaneous 
immunotherapy to treat peanut, milk and egg allergy.3 When comparing these forms of 
immunotherapy for peanut allergy, oral immunotherapy (OIT) has proven to be the most 
efficacious to date.   
  
The rationale for this study is that peanut OIT will induce immune modulation resulting in 
suppression of allergic responses allowing for desensitization to peanut and protection from 
anaphylaxis.  The use of peanut flour for this study is similar to other single allergen OIT 
studies.5 The study product will be manufactured by the University of North Carolina.  We have 
selected a dosing strategy based on all available information that is most likely to best balance 
safety with efficacy.  
  
  
4.  
Study Procedures  
  
This study will provide open label peanut OIT, with a maintenance dose of 1000 mg of peanut 
protein.  Treatment will be initiated on a single day in which multiple doses are given. Peanut 
flour will be given incrementally and increased every 15-30 minutes until a maximum dose of 6 
mg peanut protein is given. This visit may take up to 6 hours to complete:    
Initial Day Dose Escalation  
Dose #  Peanut Protein (mg)  
1  
0.8  
2  
1.5  
3  
3.0  
4  
6.0  
  
  
A minimum of 1.5mg must be achieved on the initial dose escalation day. In other studies all 
subjects have achieved at least 1.5 mg with no more than mild symptoms reaction. After the 
initial dose escalation day, subjects will return to the research unit the next day for an observed 
dose administration of the highest tolerated dose from the initial escalation day. Subjects who 
tolerate 6 mg during initial dose escalation and again on the observation day following initial 
dose escalation will proceed with dosing per the table below.  Subjects  who do not reach 6 mg 
on the initial dose escalation day  will require additional up-doing visits  to escalate to the 6 mg 
dose (Example: from 1.5 to 3.0 to 6.0 ) mg before beginning the dose build up schedule 
described below.  Once subjects have tolerated a dose under observation, they will then 
continue dosing at home with OIT and return to the research unit every 2 weeks for a 1-step 
dose escalation to a maximum daily dose of 1000 mg (see table below). Subjects may remain 
on a single-maintenance dose for longer than 2 weeks if necessary. The dosing escalations will 
be consistent with previous OIT studies. Participants who do not reach the 1000mg dose during 
the build-up phase may enter the maintenance phase at their highest tolerated dose.  Subjects 
must achieve a minimum of 200mg during the build up to enter the maintenance phase.  

Date: June 19, 2020  
Principal Investigator: Robert Wood  
Application Number: IRB00150453  
  
  
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Mild symptoms with dosing such as transient nausea, mild abdominal pain, and/or oral 
pharyngeal pruritus are common and are not considered dose limiting. Dose limiting symptoms 
include those that do not respond to antihistamine and/or require the use of epinephrine.   
  
Subjects who experience dose limiting symptoms during an up-dosing visit will continue on the 
previously tolerated dose for an additional 2 weeks. Subjects who experience dose limiting 
symptoms with a home dose will be seen in the research unit for down-dosing to the last 
tolerated dose. Subjects will remain on the last tolerated dose for at least 2 weeks before 
attempting another up-dosing. A subject may attempt a specific dose level 3 separate times 
before the dose is considered “not tolerated”. In that case, the dose previously tolerated will 
become the maintenance dose and the subject will not attempt additional up-dosing.    
  
  
  
  
  
 
Dose Build-Up Schedule  
 
Dose #  
Peanut protein  
Interval (weeks)  
% Increase  
5  
10 mg  
2  
66%  
6  
20 mg  
2  
100%  
7  
30 mg  
2  
66%  
8  
50 mg  
2  
60%  
9  
75 mg  
2  
33%  
10  
125 mg  
2  
60%  
11  
200 mg  
2  
62.5%  
12  
300 mg  
2  
33%  
13  
500 mg  
2  
60%  
14  
750 mg  
2  
50%  
15  
1000 mg  
2  
25%  
  
  
Consent will be obtained at the last visit in  IMPACT Study. For subjects who have already 
completed the last visit of that protocol and/or families who request additional time to review the 
consent, consent will be obtained at the 1st visit in the Pediatric Clinical Research Unit prior to 

Date: June 19, 2020  
Principal Investigator: Robert Wood  
Application Number: IRB00150453  
  
  
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any research specific procedures. The study will be explained in age appropriate terms to the 
participants and they will be given the opportunity to ask questions.  Some of the older subjects 
may have some context to comprehend the assent process. The assent process will be 
documented in the clinical note.  
 At each dosing visit, the following procedures will be performed prior to dose administration:  
• 
Vital signs  
• 
Review of adverse events including any accidental exposure to peanut   
• 
Review of concomitant medications  
• 
Review of home dosing diaries  
• 
Physical exam  
• 
Peak flow  
  
The build-up phase will comprise up to 22-52 weeks. Subjects will then enter the Maintenance 
phase and will continue on daily OIT at the maximum tolerated dose established during the 
Build-up phase. The Maintenance phase will consist of at least 12 weeks and may continue as 
long as through week 64. Subjects will be seen  every 6-8 weeks during the Maintenance 
phase. The window between maintenance visits may be extended to longer than 6-8 weeks if 
necessary. At the end of the Maintenance phase, subjects will undergo an open peanut oral 
food challenge to a maximum of 4000 mg of peanut protein using the following dosing regimen:  
  
Dose #  
Peanut Protein (mg)  
Cumulative Dose (mg)  
1  
100  
100  
2  
300  
400  
3  
600  
1000  
4  
1000  
2000  
5  
2000  
4000  
  
  
After this food challenge all participants will be given individualized guidelines for the 
introduction of peanut into their diet based on the outcome of the open peanut challenge.  
  
  
5.  
Inclusion/Exclusion Criteria  
  
Inclusion:  
  
1. Parent guardian must be able to understand and provide informed consent  
2. Subjects enrolled in Protocol NA_00077852 “Oral Immunotherapy for Induction of Tolerance 
in Peanut Allergic Children” who meet at least one of the following criteria:  
a. 
a reaction to a cumulative dose of ≤1000 mg of peanut protein during the End-
ofTreatment food challenge   
b. 
subjects determined to be assigned to the placebo cohort Exclusion:  

Date: June 19, 2020  
Principal Investigator: Robert Wood  
Application Number: IRB00150453  
  
  
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1. Inability or unwillingness of a parent guardian to give written informed consent or comply 
with study protocol  
2. History of severe anaphylaxis to peanut, defined by severe hypoxia, hypotension, 
neurological compromise, confusion, cardiovascular collapse, or loss of consciousness  
3. Significant chronic disease (other than asthma, rhinitis, or atopic dermatitis) requiring 
therapy; e.g., heart disease or cystic fibrosis which is judged by the investigator to have 
potential impact on study outcomes or safety.  
4. Severe or poorly controlled atopic dermatitis per investigator’s discretion   
5. Past or current history of eosinophilic gastrointestinal disease  
6. Diagnosis of asthma that meets any of the following criteria:   
• 
Uncontrolled asthma (as per Global Initiative for Asthma [GINA] latest guidelines)  
• 
History of 2 or more systemic corticosteroid courses in the last year or 1 systemic course 
within the 3 previous months prior to visit 1 for treating wheezing   
• 
Prior intubation/mechanical ventilation for asthma  
7. Currently receiving β-blocking agents, angiotensin-converting enzyme inhibitors, 
angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant therapy.   
8. Current participation in another clinical trial or participation in another clinical trial in the last 
90 days  
  
6.  
Drugs/ Substances/ Devices  
  
The treatment agent, a de-fatted peanut flour, will be provided by the University of North 
Carolina (UNC) GMP manufacturing facility under an Investigational New Drug (IND) 
application to the FDA. All study product will be obtained from the same manufacturer; a 
certificate of analysis obtained according to FDA standards will be stored as per 
manufacturer’s recommendations to ensure stability. Research staff will administer food flour to 
the subject orally in an appropriate age-appropriate food vehicle. Each peanut flour/powder is 
weighed into a separate container to be dispensed to the subject. Dosage will be done 
according to the protocol as set forth above. For home administration, the family will be 
provided with an adequate supply of individually packaged peanut OIT. The powder may be 
added to apple juice, milk, applesauce, pudding or other age-appropriate food. The product 
must be consumed promptly after mixing. If there is a prolonged delay in consumption (>2 
hours), the product should be discarded and a new product package mixed and consumed. 
Subjects or their parents will be instructed to take/administer the dose of OIT at approximately 
the same time of the day each day. At least approximately 12 hours should pass between 
doses.   
  
Drug Accountability: Under Title 21 of the Code of Federal Regulations (21CFR §312.62) the 
investigator is required to maintain adequate records of the disposition of the investigational 
agent, including the date and quantity of the drug received, to whom the drug was dispensed 
(subject-by-subject accounting), and a detailed accounting of any drug accidentally or 
deliberately destroyed. Records for receipt, storage, use, and disposition will be maintained by 
the study sites. A drug-dispensing log will be kept current for each subject. This log will contain 
the identification of each subject and the date, lot and quantity of drugs dispensed. All records 

Date: June 19, 2020  
Principal Investigator: Robert Wood  
Application Number: IRB00150453  
  
  
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regarding the disposition of the investigational products will be available for inspection by the 
IRB and FDA.  
  
7.  
Study Statistics  
  
As an open label follow-on study, statistics will be purely descriptive, describing the proportion of 
subjects achieving desensitization as well as measures of safety.    
  
Early stopping rules:  Study enrollment and treatment will be suspended pending expedited 
review of all pertinent data by the IRB and FDA if the following occur:   
• 
Any death.  
• 
More than one severe anaphylactic reaction related to peanut immunotherapy 
dosing at any stage of the protocol.  
• 
More than three subjects require 2 or more injections of epinephrine to treat one 
allergic adverse event during peanut OIT dosing.  
• 
More than 3 subjects require epinephrine on 2 or more occasions to treat 
dosingrelated reaction over the course of the study  
  
  
8.  
Risks  
  
OIT:  The primary risk of the study is related to the peanut OIT.  Previous studies have shown 
that mild reactions, such as oral pruritus, are very common, while more severe respiratory or 
systemic reactions occur in less than 1% of doses.  The dosing schema to be used on the initial 
escalation day followed by the build-up phase of immunotherapy is based on previous 
experience with peanut, egg, milk, and wheat OIT.5  In addition to acute reactions, 10-20% of 
treated subjects experience more chronic abdominal pain, which is the most common reason to 
discontinue treatment.  Some of those subjects have eosinophilic esophagitis, which has been 
estimated to occur in 2-5% of children receiving OIT.7 Subjects who persist with symptoms 
consistent with eosinophilic esophagitis such as swallowing difficulty, food impaction, persistent 
vomiting, abdominal pain, nausea and/or heartburn beyond 4 weeks of OIT avoidance will be 
referred to GI.   
Oral food challenge:  Since the subjects will have already undergone an End-of-Treatment oral 
food challenge in the IMPACT study, a baseline food challenge will not be needed to establish a 
peanut allergy diagnosis.  An end-of- treatment challenge will be conducted to determine safe 
levels of peanut to eat, but the subjects will be substantially desensitized at that time, making 
reactions less likely overall.  However, it is important to recognize that there is still risk of a 
reaction that could even be severe.  Common symptoms may include urticaria, angioedema, 
nausea, abdominal discomfort, vomiting and/or diarrhea, rhinorrhea, sneezing and/or mild 
wheezing.  The major risks involved include severe breathing difficulties, and rarely, a drop in 
blood pressure.  While a severe outcome is theoretically possible (i.e. death), this has only 
occurred once in the world in medically supervised oral food challenges.  To date the primary 
investigator has performed more than 5000 oral food challenges without a serious 
lifethreatening anaphylactic reaction or need for hospitalization  

Date: June 19, 2020  
Principal Investigator: Robert Wood  
Application Number: IRB00150453  
  
  
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Trained staff will be present to administer study food challenges and a physician will be at the 
bedside to provide oversight, evaluation, and treatment as needed.  The risks of oral food 
challenges are minimized by the following procedures:  
• 
Children must have a stable baseline examination prior to undergoing the 
challenge without significant symptoms of flaring atopic dermatitis, exacerbations 
of rhinorrhea, current urticarial, or other symptoms evaluated during food 
challenges  
• 
Children must have no wheezing or repetitive cough prior to challenge  
• 
Children must have no current illnesses (e.g. fever) at time of oral challenge  
• 
Medications (epinephrine, intravenous fluids, antihistamines, ranitidine, 
vasopressors, beta-agonists, and steroids), personnel and equipment (oxygen, 
resuscitation equipment) will be immediately available to treat allergic reactions 
should they occur.  
• 
Children will have discontinued antihistamines and bronchodilators for appropriate 
periods prior to challenge, thereby allowing investigators to perform challenges 
only when participants are stable without influence of medications.  
• 
The food will be provided gradually, at 15 minute intervals, beginning with a dose 
unlikely to trigger a reaction and progress stepwise with escalating doses.  
• 
Vital signs (heart rate, blood pressure, respiratory rate) and physical examination 
will be undertaken at baseline and as indicated throughout the challenge.  
• 
Challenges will be stopped, and medications administered, in the event of any 
objective symptoms.  
• 
Children who have experienced an allergic reaction will be observed until 2 hours 
have passed for a local reaction, or 4 hours for a generalized reaction, from the 
time of resolution of symptoms.  
  
Plan for reporting and collecting adverse events  
  
Reporting will occur as follows:   
  
i. 
Toxicity will be graded according to the NCI-CTC for application in adverse event 
reporting. The NCI-CTC has been reviewed specifically for this protocol and is 
appropriate for this study population. The purpose of using the NCI-CTC 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 
treatmentrelated toxicities. The investigator will try to determine the relationship 
of toxicity to peanut immunotherapy as not related, possibly related, or definitely 
related using standard criteria for clinical trials. All grades of toxicity will be noted. 
Toxicity grades are assigned by the study site to indicate the severity of adverse 
experiences and toxicities.   
  
ii. 
Adverse events, not included in the NCI-CTC listing, should be recorded and 
graded 1-5 according to the General Grade Definition provided below:  
  
  
  

Date: June 19, 2020  
Principal Investigator: Robert Wood  
Application Number: IRB00150453  
  
  
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Table 7: General Grade Definitions  
Grade 1  
Mild  
Transient or mild discomforts (< 48 hours), no or 
minimal medical intervention/therapy required, 
hospitalization not necessary (non-prescription or 
single-use prescription therapy may be employed to 
relieve symptoms, e.g., aspirin for simple headache, 
acetaminophen for post-surgical pain).  Examples of 
anticipated events include: oral/pharyngeal pruritus, 
localized hives/swelling, skin flushing and/or 
pruritus, rhinorrhea/sneezing, nasal congestion, 
occasional cough, throat discomfort, mild abdominal 
discomfort, nausea or single episode of vomiting.  
Grade 2  
Moderate  
Mild to moderate limitation in activity, some 
assistance may be needed; no or minimal 
intervention/therapy required, hospitalization 
possible. Examples of anticipated events  include: 
systemic hives, throat tightness without hoarseness, 
persistent cough, wheezing without dyspnea, 
persistent moderate abdominal pain/cramping/ 
nausea, repeated vomiting  
Grade 3  
Severe  
Marked limitation in activity, some assistance 
usually required; medical intervention/therapy 
required hospitalization possible. Examples of 
anticipated include: laryngeal edema, throat 
tightness with hoarseness, wheezing with dyspnea, 
persistent severe abdominal pain with repetitive 
vomiting, change in mental status, hypotension  
Grade 4  
Life-threatening  
Extreme limitation in activity, significant assistance 
required; significant medical/therapy intervention 
required hospitalization or hospice care probable. 
Example include any severe symptoms that do not 
respond to treatment.  
Grade 5  
Death  
Death  
All adverse events related to the experimental procedures will be reported to the DSMB and IRB 
in an expedited manner if they are Grade 3 and above in severity  Subject deaths are reportable 
within 24 hours.  The investigator will continue to follow or obtain documentation of the 
resolution course of such an event.  A copy of the annual DSMB report of all adverse events will 
be reported to the IRB.   
  
Data and Safety Monitoring:   
  

Date: June 19, 2020  
Principal Investigator: Robert Wood  
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A Data Safety Monitoring Board will be convened for overview of this study.  The Principal 
Investigator and Co-Investigators are responsible for collecting and recoding all clinical data.  As 
these results are collected, all toxicities and adverse events will be identified and reported to the 
PI.  Adverse events will be reported as described above.  The Principal Investigator will 
determine the relationship of the event to the study intervention and decide the course of action 
for the study participant.   
  
The use of epinephrine to treat dosing-related symptoms will be classified as a serious adverse 
event. The location of the event (home or clinic) and number of doses of epinephrine will be 
reported to the DSMB.  
  
Any new diagnosis of eosinophilic esophagitis made during the treatment period will be 
classified as a serious adverse event and reported to the DSMB.   
  
Yearly reports will be made to the DSMB and proper Institutional Committees, as required.  All 
adverse events will be kept in a computerized file by numerical identifier.   
  
In the event that the study is stopped because of adverse event(s), it will not be resumed until 
information regarding the adverse event(s) has been discussed with the DSMB and the DSMB 
concurs with resumption of the studies.   
  
  
Legal risks such as the risks that would be associated with breach of confidentiality.  
  
The risk of breach of confidentiality will be minimized by using unique identifiers for participants 
and keeping the record that links the identifier to the participant in a locked file cabinet 
accessible only to the investigators.  
  
  
Financial risks to the participants.  
  
The study does not provide routine care or any medications or treatments for general health or 
allergic problems (although we will be available for phone consultation regarding possible 
reactions).  All costs associated with study visits, skin testing, spirometry, blood drawing, food 
challenges, and OIT protein are covered by the investigators.  All participants will be required to 
provide a food matrix (juice, milk, applesauce, pudding or other age-appropriate food ) to 
consume the daily doses at home .  This will be provided by the family so that flavor/variety can 
be altered for each child’s preference.  All participants will be required to have an epinephrine 
auto-injector available at home during immunotherapy treatment.  If they do not already have 
one, they will be responsible for the cost of this medication.  
  
9.  
Benefits  
  
The benefits for the participant include the possibility of a change in sensitivity to peanut and 
decreased allergic reactions following an accidental ingestion of peanut.  Another possible 
benefit is the possibility of altering the natural course of the peanut allergy, including tolerance to 
peanut protein in someone that is unlikely to naturally “outgrown” his/her allergy.  If tolerance is 
achieved, this then make impact quality of life.  

Date: June 19, 2020  
Principal Investigator: Robert Wood  
Application Number: IRB00150453  
  
  
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10.  
Payment and Remuneration  
  
Subjects will receive a parking coupon for each visit.  
  
11.  
Costs  
  
The study does not provide routine care or any medications or treatments for general health or 
allergic problems (although we will be available 24 hours a day for phone consultation regarding 
possible reactions).  All participants will be required to have an epinephrine autoinjector 
available at home during immunotherapy treatment.  If they do not already have one, they will 
be responsible for the cost of this medication.  All costs associated with study visits and OIT are 
covered by the investigator.    
  
  
References  
  
1. 
Sampson HW, Munoz-Furlong A, Campbell RE, et al. Second symposium on the definition and 
management of ananphylaxis: Summary report: Second National Institute of Allergy and Infectious 
diseases/Food Allergy and Anaphalxis Network symposium. J Allergy Clin Immuno. 2006;92:397-403.  
2. 
Boyce JA, Assa'a A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the 
United States: summary of the NIAID-Sponsored Expert Panel Report. Nutrition (Burbank, Los Angeles 
County, Calif). 2011;27(2):253-267.  
3. 
Sicherer SH, Sampson HA. Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment. J Allergy 
Clin Immunol. 2014;133(2):291-307; quiz 308.  
4. 
Wood RA. Oral Immunotherapy for Food Allergy. Curr Allergy Asthma Rep. 2016;36(1):55-69.  
5. 
Narisety SD, Frischmeyer-Guerrerio PA, Keet CA, et al. A randomized, double-blind, placebo-controlled 
pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. J Allergy Clin 
Immunol. 2015;135(5):1275-1282 e1271-1276.  
6. 
Wood RA. Food allergen immunotherapy: Current status and prospects for the future. Journal of Allergy 
and Clinical Immunology. 2016;137(4):973-982.  
7. 
Lucendo AJ, Arias A, Tenias JM. Relation between eosinophilic esophagitis and oral immunotherapy for 
food allergy: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2014;113(6):624-629.