Randomised, controlled trial evaluating the effectiveness of probiotic and egg oral immunotherapy at inducing desensitisation or tolerance in participants with egg allergy compared with placebo (Probiotic Egg Allergen Oral Immunotherapy for Treatment of Egg Allergy: PEAT study).
A phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg oral immunotherapy at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo (Probiotic Egg Allergen Oral Immunotherapy for Treatment of Egg Allergy: PEAT study).
Murdoch Children's Research Institute
80 participants
Oct 14, 2019
Interventional
Conditions
Summary
The primary purpose of the study is to evaluate the efficacy of probiotic and egg oral immunotherapy compared to placebo in achieving sustained unresponsiveness in participants with egg allergy 8 weeks after end-of-treatment. The trial will include proven egg allergic people from 5 to 30 years of age. They will be randomised 1:1 into active and placebo groups. This study is expected to run for 6 years from the start of participant screening to the last participant finishing the study. The length of the treatment period for each participant is 18 months and the follow up period is 3 years. The discovery of a safe and tolerable treatment for food allergy will have great public health benefit.
Eligibility
Inclusion Criteria3
- Subjects are eligible for the study if they meet all of the following criteria:
- Aged between 5 and 30 years of age
- Confirmed diagnosis of egg allergy as defined by a failed DBPCFC and a positive SPT or sIgE to egg at screening
Exclusion Criteria19
- Subjects are not eligible for the study if they meet any of the following criteria:
- Subjects who are on an egg ladder diet (except baked egg)
- History of severe anaphylaxis (as defined by persistent hypotension, collapse, loss of consciousness, persistent hypoxia or ever needing more than three (3) doses of intramuscular adrenaline (epinephrine) or an intravenous adrenaline (epinephrine) infusion for management of an allergic reaction)
- Severe anaphylaxis during the study entry DBPCFC (defined as persistent hypotension, collapse, loss of consciousness, persistent hypoxia, or requiring more than 3 doses of intramuscular adrenaline (epinephrine) or an intravenous adrenaline (epinephrine) infusion for management of an allergic reaction)
- FEV1 less than 85% predicted at rest and FEV1/FVC is less than or equal to 85% predicted at rest (for those participants able to perform spirometry testing) or ongoing chronic persistent asthma (as per Australian Asthma Foundation guidelines)
- Underlying medical conditions (e.g. cardiac disease) that increase the risks associated with anaphylaxis
- Use of beta-blockers, and ACE inhibitors
- Inflammatory intestinal conditions, indwelling catheters, gastrostomies, immune-compromised states, post-cardiac and/or gastrointestinal tract surgery, critically-ill and those requiring prolonged hospitalisation or other conditions that may increase the risks of probiotic associated sepsis
- Already taking probiotic supplements or food containing probiotics in the last month.
- Reacting to the placebo component during the study entry DBPCFC
- Have received other food immunotherapy treatment in the preceding 12 months
- Currently taking immunomodulatory therapy (including allergen immunotherapy)
- Past or current major illness that in the opinion of the Site Investigator may affect the subject’s ability to participate in the study e.g. increased risk to the participant
- History of suspected or biopsy-confirmed eosinophilic oesophagitis (EoE)
- Subjects who in the opinion of the Site Investigator are unable to follow the protocol
- Another family member already enrolled in the trial (to maintain safety and blinding)
- Non-English speaking participants and families
- Participants 18 years or over (RCH site only)
- NOTE: participants with other food allergies are NOT excluded from participating in this trial.
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Interventions
Participants will be randomised 1:1 into an active (probiotic and egg immunotherapy) or placebo arm (placebo). The study consists of: - Screening visit occurs within 1 month prior to Rush Induction Day (T0). T0 Rush Induction is day 1 of treatment. - On Rush day, all participants receive increasing doses of egg (or placebo) oral immunotherapy (OIT) every 20 minutes to reach a final dose of egg white protein or placebo, beginning at 0.4 mg. - Nutritional services or an individual independent of the study will prepare the Rush doses. - Egg white protein (or placebo) will be mixed with any food (excluding foods that contain egg) the participant enjoys. - A single dose of probiotic or placebo (one standardised scoop mixed into water, at a temperature NOT exceeding 38°C) and is to be given immediately prior to the egg / placebo dosing. - Participants will be monitored (including vital signs and general nursing assessment of the skin and chest) for 2 hours after the last dose during the Rush Phase. - The study doctor and study nurse will always be present during the Rush Induction. - The Rush Induction will be performed in hospital. - Spirometry or peak flow will be performed on all participants aged 8 or older, and younger participants who are capable of doing spirometry reproducibly, before the participant receives their first dose of egg oral immunotherapy of Day 1 Rush Induction. - Participants who complete the Rush protocol without reaction will commence the Buildup Phase at a daily dose of egg white protein on the day after the Rush Induction day. - If a participant reacts to one of the doses during Rush Induction, the Rush schedule will be ceased, and the participant will commence the Buildup Phase at the dose immediately below the reaction-eliciting dose starting on the day after the Rush Induction day. - The remaining Rush doses that were not completed on day 1 will be incorporated into the Buildup phase (modified Buildup schedule for that subject) and subsequent incremental dose increases will proceed through all remaining doses of the Rush schedule followed by the doses in the Buildup schedule. - For example, if a reaction occurs following dose 3, the participant will commence the Buildup phase at the dose 2 amount and will be instructed to start this reduced dose on the following day). BUILDUP Phase -During Buildup, the daily dose of egg oral immunotherapy (OIT) (or placebo OIT) is increased every 2 weeks until the maintenance dose is reached. -Each dose increase will be administered in hospital under medical supervision. -Hospital visits for dose increases (Updose visits) will be scheduled every 2 weeks (except in unavoidable circumstances when a window of +/- 7 days is allowed). Where indicated, dose adjustments will result in deferment of a dose increase to the next scheduled visit. -Egg white protein (or placebo) will be mixed with food the participant enjoys. -A single dose of probiotic or placebo (one standardised scoop mixed into water, at a temperature NOT exceeding 38°C) is given once daily prior to the OIT treatment. -Subjects will be monitored for 2 hours after the treatment has been administered. MAINTENANCE Phase - During Maintenance, participants take a daily top dose (1870 mg) of egg white protein (or placebo) and a daily dose of probiotic or placebo at home and continue until a total of 18 months treatment is completed. - Total duration of study treatment is 18 months with no minimum duration of maintenance phase. T1 - One Day after final day of maintenance treatment T2 - 8 weeks after final day of maintenance treatment Safety follow up (phone call) 30 days (+/- 7 days) after T2 STRATEGIES TO MONITOR ADHERENCE - Participants will be required to fill in a diary every day to monitor compliance and reactions. - Pharmacy also count the returned study product to ensure compliance. MONITORING Phase Subjects will remain blinded to their PEAT treatment allocation and will continue with egg avoidance / ingestion according to the instructions they received at the T1 or T2 visits as outlined below: • Subjects who pass T1 and T2 DBPCFC visits will be classified as achieving SU and will be instructed to introduce egg into their diets ad libitum without specific instructions on how often or how much egg to ingest. • Subjects who fail T1 or T2 DBPCFC visits will be classified as allergic, and will be instructed to continue with strict egg avoidance. All subjects will be monitored for 36 months (from end-of-treatment to 36 months post-treatment). During this time, all subjects will be monitored for information on exposure to egg/amount of egg being eaten and allergic reactions via a smartphone diary application (app) or paper diary until the end of study (36 months post-treatment (T6)). A visit for SPT, bloods, and stool will be administered at the following time points: • Time point T3 – 12 months after end-of-treatment • Time point T4 – 24 months after end-of-treatment • Time point T5 – 36 months after end-of-treatment Note: Where a face-to-face visit is not possible, the visit will be conducted by phone and SPT, bloods and stool test will not be performed
Locations(2)
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ACTRN12619000480189