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Trial registered on ANZCTR


Registration number
ACTRN12621001001886
Ethics application status
Approved
Date submitted
15/06/2021
Date registered
30/07/2021
Date last updated
27/04/2023
Date data sharing statement initially provided
30/07/2021
Date results information initially provided
27/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Early Peanut Immunotherapy in Children (EPIC) - a trial of peanut oral immunotherapy to induce desensitisation in preschool aged children with a peanut allergy.
Scientific title
A pragmatic, open-label, randomised study of peanut oral immunotherapy in inducing desensitisation in children under 5 years of age with peanut allergy, when compared to standard care (strict peanut avoidance).
Secondary ID [1] 303814 0
NA
Universal Trial Number (UTN)
Trial acronym
EPIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peanut Allergy 321793 0
Condition category
Condition code
Inflammatory and Immune System 319519 319519 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention group = peanut oral immunotherapy (OIT) taken daily for 12 months

The intervention will consist of incrementally increasing doses of defatted peanut flour administered daily over a period of 12 months.

The intervention product is Peanut Butter & Co Pure Peanut peanut powder, distributed by Peanut Butter & Co, New York, USA. The intervention product is a routinely available food product with a single ingredient, defatted peanut flour (50% protein by weight). The peanut flour/powder will be provided to each participant in a jar, which will be used by parents to make up their own daily dosing at home, using study provided measuring spoons and instructions. Daily doses of peanut flour will be mixed into the child's food of choice, which can be varied throughout the study to mimic normal feeding habits.

Peanut OIT dosing schedule consists of three phases:

1. Treatment Initiation (TI)
The first day of treatment participants will undertake a treatment initiation visit where subjects receive up to 4 increasing doses of peanut flour every 20 minutes to reach a final dose of 15mg peanut protein (1mg, 3mg, 10mg, 15mg peanut protein). Research nurses will prepare the doses of TI mixed into the participants own food (yoghurt/ice-cream). If a subject reacts during TI, the next day they will commence dosing at home with the dose immediately below the one that provoked onset of symptoms. Any remaining doses not completed during treatment initiation will be incorporated into the up-dosing phase. If all doses are tolerated during TI, participants will commence dosing at home with 15mg peanut protein.

2. Up-dosing Phase
Following TI participants will continue on the same dose at home daily for 2 weeks. Up-dosing will occur approximately every 2 weeks until a maximum dose of 360 mg peanut protein (3/8 tsp peanut flour) is reached (15 mg, 30 mg, 60 mg, 120 mg, 180 mg, 240 mg, 360 mg of peanut protein).

3. Maintenance Phase
Participants will continue to take daily doses of 360 mg peanut protein (3/8 tsp peanut flour) until a total of 12 months of treatment is completed (calculated from date of TI visit).

Compliance and Adverse Events
Parents will use an electronic daily diary based in the REDCap platform to record information about their daily dosing and any adverse events they experience. Side effects are common with OIT, and it is anticipated that some children will experience mild (pruritus, swelling or rash, abdominal discomfort or other transient symptoms), moderate ( persistent hives, increased abdominal discomfort/ increased vomiting) and severe (anaphylaxis) allergic reactions to their peanut OIT. All adverse events will be recorded in the electronic diary and monitored by study staff.

If allergic symptoms develop following a dose of OIT at home, the parent or guardian will treat the symptoms in line with their prescribed Allergy Action Plan, using rescue medication as required. For any ongoing symptoms, or sudden onset of severe symptoms the families will be requested to alert study staff. The site investigators will decide based on the nature of the symptoms, the plan for continuation of dosing (including plans for reintroduction of dosing and/or extending the period of time before the next up-dose). If ongoing symptoms are noted, the use of antihistamine or another medication for prophylaxis may be initiated by the study team.

If anaphylaxis symptoms develop during home dosing (eg wheeze, stridor, difficulty breathing, transient hypotension), then the immediate next dose will be reduced by half. The family will be counselled and debriefed on the management of the anaphylaxis and the next dose will be given at home, or via an unscheduled visit.
Intervention code [1] 320446 0
Treatment: Other
Comparator / control treatment
Control group = standard care (i.e. strict peanut avoidance) for 12 months with no additional treatment

The control group will continue strict peanut avoidance, and will not receive any interventional product during the study.
Control group
Active

Outcomes
Primary outcome [1] 327388 0
The primary outcome measure is the proportion of participants with a peanut eliciting dose of greater than 600mg peanut protein at end of treatment compared between the peanut OIT and control group, which will be assessed using an oral food challenge with peanut at the end of treatment.

Timepoint [1] 327388 0
12 months after commencing peanut OIT
Secondary outcome [1] 394901 0
To describe the safety of the proposed peanut OIT treatment we will report the proportion of participants who experience treatment related adverse events, including severity and frequency of such events.

All participants will be monitored for AEs from when they sign the consent form up until the end of treatment visit. AEs that occur during on site study visits will be recorded by study staff at the time they occur in the source document. Possible adverse events will also be elicited from participants’ parents via the daily eDiary.

All safety events will be categorised as either:
• Treatment related events
• Food challenge related events
• Accidental food consumption events
• Other adverse events (not related to previous categories)

The causal relationship of the AE to peanut OIT will be attributed by the Investigator or delegate and recorded in the source document, with the following criteria used for guidance:
Related:
• Follows a clear temporal sequence from administration of OIT (e.g. within 1 hour)
• Has no other possible explanation
• Improves on cessation or reduction in dose of OIT (positive de-challenge)
• Recurs or worsens upon recommencing or increasing dose of OIT (positive re-challenge)
Probable:
• Follows a reasonable temporal sequence from administration of OIT (e.g. within 4 hours).
• Could not be reasonably explained by other factors.
• Is a known side effect and/or follows a known pattern of reactions to OIT.
• Positive de-challenge and/or re-challenge
Possible:
• Follows a reasonable temporal sequence from administration of OIT (e.g. within 4 hours).
• Is a known side effect or follows an expected pattern of symptoms following OIT but could be reasonably explained by other factors
Unlikely:
• Does not follow a reasonable temporal sequence from administration of OIT.
• Could be reasonably explained by other factors.
• Does not demonstrate a positive de-challenge / rechallenge
Not related:
• The AE does not meet the above criteria
• There is sufficient information that the AE is not related to OIT.

The severity of each AE will be assessed by the investigator using the following categories and recorded in the source document.
• Mild: The AE was transient and easily tolerated by the subject
• Moderate: The AE caused discomfort and interference with the subject’s general condition
• Severe: The AE caused considerable interference with the subject’s general condition and may have been incapacitating.
Anaphylaxis and allergic reactions will be graded in accordance with the National Institute of Allergy and Infectious Diseases (NIAID)
Timepoint [1] 394901 0
12 months after commencing peanut OIT
Secondary outcome [2] 394902 0
The tolerability of the proposed peanut OIT treatment will be assessed using the proportion of participants who discontinue peanut OIT treatment due to treatment related adverse events. This will be assessed using eCRF data for the number and proportion of participants who discontinue treatment as well as the reason for discontinuation will be reported (treatment-related adverse events; lack of participant compliance e.g. refusing to take doses; family preference or unable to adhere to requirements; perceived lack of efficacy; investigator direction; other)
Timepoint [2] 394902 0
At the conclusion of study.
Secondary outcome [3] 394903 0
To compare the change in immunological markers of peanut sensitisation from baseline to EOT between the peanut OIT and control groups, we will utilise peanut sIgE (ImmunoCAP system, Thermo Fisher Scientific) and peanut SPT performed at baseline (SV1) and EOT.
Timepoint [3] 394903 0
12 months after commencing peanut OIT
Secondary outcome [4] 394904 0
We will compare the change in quality of life from baseline to end of treatment between the peanut OIT and control groups using the validated FAQLQ-PF, FAQL-PB and FASE-P at baseline and within the week prior to end of treatment challenge. A participant’s data will be eligible for inclusion in this secondary outcome analysis if the questionnaire is completed at both time points.
Timepoint [4] 394904 0
12 months after commencing peanut OIT
Secondary outcome [5] 394905 0
To compare the proportion of children with an eliciting dose of at least 300mg peanut protein at end of treatment in the peanut OIT and control groups using an oral food challenge to peanut.
Timepoint [5] 394905 0
12 months after commencing peanut OIT
Secondary outcome [6] 394906 0
To compare the proportion of children who tolerate a full serve (2500mg) of peanut without reaction at end of treatment in the peanut OIT and control groups assessed during an oral food challenge to peanut.
Timepoint [6] 394906 0
12 months after commencing peanut OIT
Secondary outcome [7] 397768 0
Parental perceptions of OIT will be assessed by calculating the Net Promoter Score (NPS) at baseline, 12 weeks and 12 months in intervention and control participants. The NPS is calculated by first determining the percentage of Promoters (score 9-10), Neutrals (score 7-8) and Detractors (score 0-6), and then subtracting the percentage of Detractors from the percentage of Promoters to give a value of between -100 and +100.
Timepoint [7] 397768 0
12 months after commencing peanut OIT
Secondary outcome [8] 397769 0
To compare the proportion of children with an eliciting dose of at least 600mg peanut protein at end of treatment in the peanut OIT and control groups using an oral food challenge to peanut.
Timepoint [8] 397769 0
12 months after commencing peanut OIT.

Eligibility
Key inclusion criteria
1) Male or female children from 1-4 years of age (i.e. first visit to occur on or after the
participant’s first birthday, and prior to their fifth birthday).
2) Diagnosis or suspicion of peanut allergy in a child currently following a peanut
exclusion diet.
3) Confirmed or highly probable peanut allergy, defined as
a) Confirmed: positive peanut skin prick test (mean wheal diameter >3mm) or
specific IgE (>0.35 kU/L) at SV1 and allergic reaction during the entry peanut OFC
which meets the stopping criteria
b) Highly probable: previous clinical history of allergic reaction to peanut with
unequivocal symptoms meeting stopping criteria and at least 1 of the following:
i) Peanut skin prick test mean wheal diameter at SV1 >8mm
ii) Peanut sIgE at SV1 >15 kU/L
iii) Ara h 2 sIgE at SV1 >1 kU/L
c) Highly probable: equivocal or no clinical history of allergic reaction to peanut with
at least 2 of the following:
i) Peanut skin prick test mean wheal diameter at SV1 >8mm
ii) Peanut sIgE at SV1 >15 kU/L
iii) Ara h 2 sIgE at SV1 >1 kU/L
4) Parents/guardians and subjects willing to comply with all the study requirements
during their participation in the study.
Minimum age
1 Years
Maximum age
5 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) History of severe anaphylaxis to peanut prior to study entry, defined as a reaction
causing loss of consciousness, persistent hypoxia, or requiring three or more doses of
IM adrenaline, an IV adrenaline infusion or intubation for management of an allergic
reaction.
2) Use of beta-blockers
3) Participants receiving immunotherapy for food allergy, or who have received
immunotherapy for food allergy in the preceding 3 months.
4) Participants currently receiving other allergen immunotherapy
5) Children with significant underlying medical conditions that place them at increased
risk of adverse outcomes in the event of an allergic reaction, such as cardiovascular or
respiratory diseases. A study doctor will review these children before enrolling them
in the study.
6) Persistent, uncontrolled asthma or wheezing episodes.
7) Subjects who in the opinion of the investigator will be unable to follow the protocol

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by REDCap computer software. Stratification is conducted based on age (<2) and Skin Prick Test (SPT) size (>8).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
We will perform between group comparisons for each primary and secondary outcome at the end of the study at 12 months and a significance threshold of 0.05 will be used.
Statistical analysis and preparation of graphics will be performed in STATA. The primary outcome will be analysed by comparison of proportion of desensitised patients in each group using chi-square test at a significance level of 0.05. Participants who withdraw or do not complete 12 month OFC will be defined as treatment failures. Secondary outcomes including QoL, SPT and specific IgE measurements and number of adverse events are all continuous variables, and will be compared between groups using independent t tests with a log-transformation of the data if required. Effects on outcome of baseline characteristics (presence of other allergic disease, age, sex) will be explored using logistic and linear regression as appropriate. Change in these measurements from baseline to end of treatment will be compared using paired sample t-tests (or non-parametric equivalent, where relevant). Alpha will be set at 0.05.

Sample Size
Based on existing published data, we anticipate that two-thirds (66%) of participants randomised to the intervention will achieve the primary outcome by intention-to-treat analysis. We estimate that 25% of the control group will meet the primary outcome, due to either coincidental high reaction threshold, spontaneous resolution of allergy. We will randomise participants at a ratio of 1 intervention to 1 control. A sample size of 50 randomised participants (25 intervention, 25 controls) will have power of 0.85 to detect the estimated difference between groups (66% in the intervention compared to 25% in controls) with an alpha of 0.05.


Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
15/08/2021
Actual
14/09/2021
Date of last participant enrolment
Anticipated
30/09/2022
Actual
13/09/2022
Date of last data collection
Anticipated
30/10/2023
Actual
Sample size
Target
50
Accrual to date
Final
52
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 19254 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 33834 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 308212 0
Government body
Name [1] 308212 0
Government of Western Australia Department of Health
Country [1] 308212 0
Australia
Primary sponsor type
Government body
Name
Child and Adolescent Health Service
Address
Level 5, Perth Children's Hospital, 15 Hospital Avenue, Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 308997 0
None
Name [1] 308997 0
NA
Address [1] 308997 0
NA
Country [1] 308997 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308193 0
Child and Adolescent Health Service
Ethics committee address [1] 308193 0
Level 5, Perth Children's Hospital, 15 Hospital Avenue, Nedlands WA 6009
Ethics committee country [1] 308193 0
Australia
Date submitted for ethics approval [1] 308193 0
19/01/2021
Approval date [1] 308193 0
31/03/2021
Ethics approval number [1] 308193 0
RGS0000004384

Summary
Brief summary
The EPIC study is a randomised controlled trial (RCT) to establish the efficacy, safety and tolerability of a pragmatic peanut oral immunotherapy (OIT) protocol in children under 5 years of age in WA. We hypothesise that low dose peanut OIT in young preschool aged children will be effective and tolerable.

Participants with peanut allergy will be randomised 1:1 to receive either peanut OIT or standard care (peanut avoidance) for 12 months. The OIT program consists of a daily dose of peanut flour incrementally increased under medical supervision every 2 weeks until a maintenance peanut protein dose of equivalent to approximately 1.5 peanuts is reached.

After 12 months, all participants will have an oral food challenge (OFC) to establish their peanut eliciting dose, which will be defined as the amount of peanut they can consume before having an allergic reaction. We will compare the eliciting dose between participants receiving OIT and controls to determine the efficacy of peanut OIT. We will also collect and report quality of life and adverse event data to assess efficacy, safety and tolerability of this treatment.

With this project, we are responding to an area of unmet need and consumer demand to provide access to food allergy treatments in Australia that are currently available overseas, using a translatable approach that could be applied to other foods and underpin a future national approach to food OIT.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109878 0
Dr Michael O'Sullivan
Address 109878 0
Immunology Department
Perth Children’s Hospital
15 Hospital Avenue, Nedlands, WA, 6009
Country 109878 0
Australia
Phone 109878 0
+61 434 582 982
Fax 109878 0
Email 109878 0
Michael.O'[email protected]
Contact person for public queries
Name 109879 0
Dr Michael O'Sullivan
Address 109879 0
Immunology Department
Perth Children’s Hospital
15 Hospital Avenue, Nedlands, WA, 6009
Country 109879 0
Australia
Phone 109879 0
+61 434 582 982
Fax 109879 0
Email 109879 0
Michael.O'[email protected]
Contact person for scientific queries
Name 109880 0
Dr Michael O'Sullivan
Address 109880 0
Immunology Department
Perth Children’s Hospital
15 Hospital Avenue, Nedlands, WA, 6009
Country 109880 0
Australia
Phone 109880 0
+61 434 582 982
Fax 109880 0
Email 109880 0
Michael.O'[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEarly Peanut Immunotherapy in Children (EPIC) trial: Protocol for a pragmatic randomised controlled trial of peanut oral immunotherapy in children under 5 years of age.2023https://dx.doi.org/10.1136/bmjpo-2023-002294
N.B. These documents automatically identified may not have been verified by the study sponsor.