Low Dose Multi-Nut Oral Immunotherapy in Pre-schoolers With a Multi-Nut Allergy

NCT05049512 | Completed DMC

• 1 other identifier: 74540
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The LMNOP trial will be a 2-armed, open-label, randomised controlled trial (RCT), 2:1. Over a period of 18 months, children in the Multi-Nut Oral Immunotherapy Treatment (OIT) Group (experimental arm) will undergo low dose OIT to two nuts they are allergic to. At this time, children in the Standard Care Group (control arm) will be instructed to strictly avoid consuming two nuts they are allergic to. Avoiding consuming nut allergens is the standard care advice for children with peanut/tree nut allergies in Australia. The trial will assess the difference in the proportion of participants undergoing Multi-Nut OIT who can achieve sustained unresponsiveness (SU) compared to the proportion of participants avoiding nuts who develop natural tolerance (NT), i.e. grow out of their allergy. SU is when a participant can pass an oral food challenge (OFC) after having paused OIT treatment for several weeks. Participants will be between the ages of 18 and 36 months at the time of screening. The first 12 participants enrolled will be part of the pilot phase, with a total of n = 45 for the main trial. It is hypothesised that there will be a higher proportion of participants in the Multi-Nut OIT Group versus the Standard Care Group who pass the OFC following the 18-month treatment phase. That is, a higher proportion of participants in the Multi-Nut OIT Group will achieve SU compared to participants in the Standard Care Group achieving NT.

Conditions

Allergy, Nut

Keywords

Oral immunotherapy; Randomised controlled trial; Skin prick test; Oral food challenge

Outcome Measures

Primary Outcomes (1)

• Main Trial: Comparison of the number of participants who pass their OFC after the 18-month treatment phase for both study nuts between the Multi-Nut OIT Group and Standard Care Group

  In both groups, passing requires participants tolerating all OFC doses for both of their study nuts. For the Multi-Nut OIT Group, participants must pass their OFC at the end of the 18-month treatment phase, and then pass another OFC after 4 weeks of no OIT. For the Standard Care Group, participants must pass their OFC after the 18-month period. Participants have a personalised combination of two nuts: a. peanut, b. almond, c. cashew, d. hazelnut, e. walnut, as nominated at study screening.

  At 18 months post commencement of treatment

Secondary Outcomes (35)

• Main Trial: Difference between the Multi-nut OIT Group in comparison to the Standard Care Group in the proportion and severity of reported adverse events (AE) related to study nut ingestion during the 18-month treatment phase

  During the 18-month treatment phase

• Main Trial: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in mean change from screening to 18 months in quality of life scores for the children, measured by the Food Allergy Quality of Life-Parent Form (FAQL-PF)

  Screening and at 18 months

• Main Trial: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in mean change from screening to 18 months in quality of life scores for the parents using the ICEpop CAPability measure for Adults (ICECAP-A)

  Screening and at 18 months

• Main Trial: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in mean change from screening to 18 months in State/Trait anxiety using the State/Trait Anxiety Inventory (STAI)

  Screening and at 18 months

• Main Trial: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in the number of allergy-related healthcare visits from randomisation to 18 months

  Randomisation to 18 months

Study Arms (2)

Multi-nut OIT

EXPERIMENTAL

Participants will have a personalised combination of two nuts they are allergic to for their multi-nut OIT (a. peanut, b. almond, c. cashew, d. hazelnut, e. walnut). In the escalation visit, participants will receive 5 increasing doses of personalised multi-nut OIT in clinic at 20-minute intervals: 1 mg, 3 mg, 6 mg, 12 mg, 24 mg total nut protein, 12 mg/nut. The build-up phase will consist of daily home doses of multi-nut OIT and clinic visits every 2 weeks for up-dosing, up to a maintenance dose of 600 mg total protein, 300 mg/nut, over 3-8 months. In the maintenance phase, participants will continue to take their multi-nut OIT dose of 600 mg total protein each day at home for the remainder of the 18 months, with visits to the clinic every 3 months.

Other: Multi-nut OIT

Standard Care

NO INTERVENTION

Strict avoidance of the 2 study nuts the participants are allergic to over 18 months - a. peanut, b. almond, c. cashew, d. hazelnut, e. walnut, as per standard care instructions for children with allergies in Australia.

Interventions

Multi-nut OIT OTHER

Finely ground pure peanut, almond, cashew, hazelnut, and walnut.

Multi-nut OIT

Eligibility Criteria

• Age: 18 Months - 36 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Is between the ages of 18 and 36 months at the time of Screening visit 1
• Has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf
• IgE-mediated allergy to 2 of peanut, almond, cashew, hazelnut or walnut, confirmed by:
• Nut 1 pre-screening:
• For at least one of almond, cashew, hazelnut or walnut (Nut 1)\*:
• History of ingestion with IgE-mediated reaction (birth to present) AND
• History of SPT ≥3mm OR History of sIgE ≥0.35 number of kilounits per liter (KuL) AND
• Nut 2 pre-screening:
• For a second nut out of peanut, almond, cashew, hazelnut or walnut (Nut 2):
• History of SPT ≥3mm OR History sIgE ≥0.35 KuL
• In clinic screening: Participants meeting pre-screening criteria for Nuts 1 and 2 above will be invited for in-clinic screening
• SPT: wheal size ≥3mm at Visit 1 for 2 of peanut, almond, cashew, hazelnut or walnut AND
• OFC: react to ≤3000 mg protein top dose (4449 mg cumulative) in open, single nut OFC for 2 of peanut, almond, cashew, hazelnut or walnut
• OFC not needed if:
• History of failed OFC within past 3 months (confirmed by investigator review of discharge summary) OR History of anaphylaxis after ingestion within past 3 months based on investigator judgement +/- review of ER/Ambulance/medical notes

You may not qualify if:

• History of severe anaphylaxis (as defined by persistent hypotension, collapse, loss of consciousness, persistent hypoxia or ever needing more than 2 doses of intramuscular adrenaline or an intravenous adrenaline infusion for management of an allergic reaction)
• Severe anaphylaxis at study screening OFC (defined as persistent hypotension, collapse, loss of consciousness, persistent hypoxia, or requiring more than 2 doses of intramuscular adrenaline or an intravenous adrenaline infusion for management of an allergic reaction)
• Fails either screening OFC on dose 1 (0.5 mg).
• Underlying medical conditions that increase the risks associated with anaphylaxis (e.g., cardiac disease or poorly controlled asthma (defined below))
• Confirmed eosinophilic esophagitis (EoE) or history indicating EoE
• Current use of beta-blockers or angiotensin-converting enzyme (ACE) inhibitors
• Receiving systemic immunomodulatory treatment
• Not commenced or unable to eat solid food
• Weight \<7.5kgs (recommended minimum weight for EpiPen Jr (adrenaline autoinjector))
• Has a sibling in the study
• Defining uncontrolled asthma (Global Initiative for Asthma. Asthma management and prevention for adults and children older than 5 years)
• In the past 4 weeks, has the patient had:
• Daytime symptoms more than twice/week? Any night waking due to asthma? Short Acting Beta Agonist (SABA) reliever needed more than twice/week? Any activity limitation due to asthma? Uncontrolled - answered yes to 3-4 of these

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead

Study Sites (1)

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

MeSH Terms

Conditions

Nut Hypersensitivity

Condition Hierarchy (Ancestors)

Nut and Peanut Hypersensitivity; Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Kirsten Perrett, MBBS FRACP

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2021
• First Posted: September 20, 2021
• Study Start: November 16, 2021
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Six months after the publication of the primary outcome
• Access Criteria: Prior to releasing any data, the following are required: a data access agreement must be signed between relevant parties; the LMNOP trial investigators must see and approve the analysis plan describing how the data will be analysed; there must be an agreement around appropriate acknowledgment; and any additional costs involved must be covered.

Locations

AU (1)