Analysing HIgh Dose Probiotic Peanut Oral Immunotherapy (PPOIT) and High Dose Peanut Oral Immunotherapy (OIT) Versus LOw Dose Peanut OIT for Peanut Allergy (HILO)

This study will compare the effectiveness of three different treatments to treat peanut allergy

Study Overview

• Status: Withdrawn
• Conditions: Peanut Allergy
• Intervention / Treatment: Drug: Peanut Oral Powder [PEANUT POWDER]; Dietary supplement: Probiotic (LGG®, Lactobacillus Rhamnosus) or placebo probiotic (maltodextrin)

Detailed Description

This is a three-arm, multi-centre, head-to-head randomised trial, comparing two treatments against a low dose oral immunotherapy approach for peanut allergy.

One hundred and thirty children aged 1 year to 10 years with current peanut allergy confirmed by failed double-blind placebo-controlled food challenge (DBPCFC) at study screening will be recruited for this study. Participants will be recruited from The Royal Children's Hospital Melbourne, Women's and Children's Hospital (Adelaide) and from the general community.

Participants will be randomized to:

1. High-dose rapid escalation peanut OIT combined with probiotic (HD PPOIT)
2. High-dose rapid escalation peanut OIT combined with probiotic placebo (HD OIT)
3. Low-dose slow escalation peanut OIT combined with probiotic placebo (LD OIT)

The length of the treatment period for each participant is 18 months and the post-treatment follow up period is 12 months

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5006
      • Not yet recruiting
      • Womans and Childrens Hospital
      • Contact: Michael Gold; Phone Number: +61881617000; Email: Michael.gold@adelaide.edu.au
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Recruiting
      • Murdoch Childrens Research Institute
      • Contact: Julie Burns; Phone Number: +61399366184; Email: hilo.study@mcri.edu.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 1-10 years.
• >7kg (the weight considered safe for the administration of an adrenaline injector);
• Confirmed diagnosis of peanut allergy as defined by a failed DBPCFC with peanut and a positive SPT or sIgE to peanut at screening;
• Has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf

Exclusion Criteria:

• 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 or an intravenous adrenaline 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 or an intravenous adrenaline infusion for management of an allergic reaction)
• 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 angiotensin converting enzyme (ACE) inhibitors
• 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 blinding, safety and equity of access) or in any other clinical trial from the same study group.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-dose peanut OIT combined with probiotic (HD PPOIT); High-dose rapid escalation peanut OIT combined with probiotic (HD PPOIT) taken daily for 18 months.	Drug: Peanut Oral Powder [PEANUT POWDER]; Peanut oral immunotherapy at varying doses and build-up regimes given daily for 18 months; Other Names: Peanut oral immunotherapy; Dietary supplement: Probiotic (LGG®, Lactobacillus Rhamnosus) or placebo probiotic (maltodextrin); Probiotic or placebo-probiotic given daily for 18 months
Experimental: High-dose peanut OIT combined with probiotic placebo (HD OIT); High-dose rapid escalation peanut OIT combined with probiotic placebo (HD OIT) taken daily for 18 months	Drug: Peanut Oral Powder [PEANUT POWDER]; Peanut oral immunotherapy at varying doses and build-up regimes given daily for 18 months; Other Names: Peanut oral immunotherapy; Dietary supplement: Probiotic (LGG®, Lactobacillus Rhamnosus) or placebo probiotic (maltodextrin); Probiotic or placebo-probiotic given daily for 18 months
Active Comparator: Low-dose peanut OIT combined with probiotic placebo (LD OIT); Low-dose slow escalation peanut OIT combined with probiotic placebo (LD OIT) taken daily for 18 months.	Drug: Peanut Oral Powder [PEANUT POWDER]; Peanut oral immunotherapy at varying doses and build-up regimes given daily for 18 months; Other Names: Peanut oral immunotherapy; Dietary supplement: Probiotic (LGG®, Lactobacillus Rhamnosus) or placebo probiotic (maltodextrin); Probiotic or placebo-probiotic given daily for 18 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between the treatment arms in the proportion of participants who achieve remission of peanut allergy at 8 weeks post treatment.	Remission will be assessed 8 weeks after the end of treatment timepoint and is defined as passing (completing without reaction) the double-blind placebo controlled food challenge (DBPCFC) at the end of treatment and at 8 weeks post treatment	22 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between the treatment arms in the proportion of participants who achieve full desensitisation of peanut allergy at end of treatment	Full desensitisation will be defined by participants passing (completing without reaction) the double-blind placebo controlled food challenge (DBPCFC) undertaken at the end of treatment	20 months
Difference between the treatment arms in the exposure-adjusted event rate of adverse events (AE)	The total number of treatment-related AE the participant reports during the course of treatment adjusted for the time the participant is on treatment (in years)	20 months
Difference between treatment arms in changes in Quality of Life Scores using the Food Allergy Quality of Life Questionnaires (FAQLQ).	FAQLQ total score, as well as three sub-scores (food anxiety, general emotional impact, and social and dietary limitations) will be calculated as per the instrument scoring manual	Baseline, 22weeks, 76 weeks, 84 weeks, 128 weeks
Difference between treatment arms in changes in the peanut skin prick test (SPT) wheal size.	Skin prick test to whole peanut extract	Baseline, 76 weeks, 84 weeks,128 weeks
Difference between treatment arms in change from baseline peanut specific immunoglobulin E (sIgE) levels	Blood samples will be collected and levels of sIgE against peanut will be measured by ImmunoCAP (Phadia AB, Uppsala, Sweden)	Baseline, 76 weeks, 84 weeks,128 weeks
Difference between treatment arms in adherence to treatment regime as measured by daily treatment doses taken by the participant	Adherence to treatment will be monitored by reviewing the participant diary	20 months
Difference between treatment arms in participant experience as assessed from qualitative interviews	Interview guide developed and conducted, recorded, transcribed verbatim, and responses explored using framework analysis	20 months
Difference between clinical outcome groups in cost using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS)	Captured per number of hospitalizations, Emergency room (ER) visits, General Practitioner (GP) visits and medications / number of prescriptions required. Data acquired using participant questionnaires, participant study diaries and supplemented by administrative hospital data linkage	Baseline through to 32 months
Difference between clinical outcome groups in quality adjusted life year (QALY) will be estimated at 32 months using the Food Allergy Quality of Life Form (FAQLQ) mapped to the generic health utility instrument Assessment of Quality of Life-6D (AQoL-6D)		32 months
Difference between clinical outcome groups in peanut ingestion from end of treatment to 12 months post treatment	Peanut ingestion data will be captured from the participant's study diary	20 months to 32 months
Difference between clinical outcome groups in reactions to peanut from end of treatment to 12 months post treatment	Number of reactions, symptoms experienced, and treatment administered will be captured from the participant's study diary	20 months to 32 months

Collaborators and Investigators

• Sponsor: Murdoch Childrens Research Institute
• Investigators: Principal Investigator: Paxton Loke, Murdoch Children's Research Institute

Publications and helpful links

General Publications

• Loke P, Orsini F, Lozinsky AC, Gold M, O'Sullivan MD, Quinn P, Lloyd M, Ashley SE, Pitkin S, Axelrad C, Metcalfe JR, Su EL, Tey D, Robinson MN, Allen KJ, Prescott SL, Galvin AD, Tang MLK; PPOIT-003 study group. Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial. Lancet Child Adolesc Health. 2022 Mar;6(3):171-184. doi: 10.1016/S2352-4642(22)00006-2. Epub 2022 Feb 4. Erratum In: Lancet Child Adolesc Health. 2022 May;6(5):e19. doi: 10.1016/S2352-4642(22)00097-9.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: February 29, 2024
• First Submitted That Met QC Criteria: February 29, 2024
• First Posted (Actual): March 6, 2024

Study Record Updates

• Last Update Posted (Actual): August 15, 2024
• Last Update Submitted That Met QC Criteria: August 13, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Peanut Hypersensitivity
• Other Study ID Numbers: 100992

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Beginning 24 months after article publication, the following will be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept MCRI's conditions for access (including any conditions relating to MCRI's intellectual property):

• Individual participant data that underlie the results reported in this article after de-identification (text, tables, figures and appendices)
• Trial protocol, Statistical Analysis Plan, Informed Consent Form (ICF)

• IPD Sharing Time Frame: Beginning 24 months following article publication
• IPD Sharing Access Criteria: These will be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept MCRI's conditions for access (including any conditions relating to MCRI's intellectual property)
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes