Early Peanut Immunotherapy in Children (EPIC) - a trial of peanut oral immunotherapy to induce desensitisation in preschool aged children with a peanut allergy.

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.