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Trial registered on ANZCTR


Registration number
ACTRN12619000898156
Ethics application status
Approved
Date submitted
5/06/2019
Date registered
26/06/2019
Date last updated
15/08/2024
Date data sharing statement initially provided
26/06/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Follow-on study of a multicentre randomised, controlled trial (PPOIT-003) evaluating the long-term safety and efficacy of Probiotic and Peanut Oral Immunotherapy (PPOIT) compared with Oral Immunotherapy (OIT) alone and with placebo in peanut allergic individuals
Scientific title
Follow-on study of a multicentre randomised, controlled trial (PPOIT-003) evaluating the long-term safety and efficacy of Probiotic and Peanut Oral Immunotherapy (PPOIT) compared with Oral Immunotherapy (OIT) alone and with placebo in peanut allergic individuals
Secondary ID [1] 298398 0
NIL
Universal Trial Number (UTN)
Trial acronym
PPOIT-003LT
Linked study record
This record is a follow-up study of ACTRN12616000322437 (A multicentre, randomized, controlled trial evaluating the effectiveness of Probiotic and Peanut Oral Immunotherapy (PPOIT) in inducing desensitisation or tolerance in children with peanut allergy compared with Oral Immunotherapy (OIT) alone and with placebo)

Health condition
Health condition(s) or problem(s) studied:
Peanut Allergy 313093 0
Food Allergy 313094 0
Condition category
Condition code
Inflammatory and Immune System 311578 311578 0 0
Allergies

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a multicentre follow-on study of the PPOIT-003 study (ACTRN12616000322437). There is no treatment intervention in this study.

Although it is a follow -on study, PPOIT-003LT has been approved under a separate ethics submission.

All participants who complete the PPOIT-003 will be eligible for enrolment into this follow-on study.

Subjects and study staff will remain blinded to their PPOIT-003 treatment allocation and will continue with peanut avoidance or ingestion according to the instructions they received at the end of treatment in PPOIT-003 (based upon their treatment outcome at end of treatment in PPOIT-003).

F0 (First visit):
- The following assessments will be conducted: skin prick test, medical history review, blood and stool collection, Food Allergy Quality of Life questionnaire.

F1 time point (12 months after F0 or 24 months after the final day of treatment)
- phone call will be conducted for the following:
- Allergy Questionnaire
- Food Allergy Quality of Life questionnaire
- Reminder for parent/participant to continue with diary recording (either mobile app or paper).

F2 time point (24 months after F0 or 36 months after the final day of treatment)
A visit will be conducted at this time point for the following:
• Weight/height;
• Skin prick test (peanut, egg, milk, cashew, almond, pistachio, hazelnut, dust mite and positive
and negative control);
• Blood and faecal sample (faecal sample collected by parents at home);
• Anaphylaxis education;
• Allergy questionnaire;
• Food Allergy Quality of Life-Parent Form (FAQL-PF) and age appropriate Food Allergy Quality of Life forms (i.e. participants aged 8-12 years and 13-17 years to complete Food Allergy Quality of Life-Child Form (FAQLQ-CF) and Food Allergy Quality of Life-Teenager Form (FAQLQ-TF) respectively);
Please note, in unavoidable circumstances (e.g. school camps), the window for the F2 time point can be +/- 14 days to accommodate parent/participant availability. 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.

F3 time point (36 months after F0 or 48 months after the final day of treatment)
A visit will be conducted at this time point for the following:
• Weight/height;
• Skin prick test (peanut, egg, milk, cashew, almond, pistachio, hazelnut, dust mite and positive
and negative control);
• Blood and faecal sample (faecal sample collected by parents at home);
• Anaphylaxis education;
• Allergy questionnaire;
• Food Allergy Quality of Life-Parent Form (FAQL-PF) and age appropriate Food Allergy Quality of Life forms (i.e. participants aged 8-12 years and 13-17 years to complete Food Allergy Quality of Life-Child Form (FAQLQ-CF) and Food Allergy Quality of Life-Teenager Form (FAQLQ-TF) respectively);
• Medical history as clinically indicated prior to DBPCFC or OFC;
• Double blind, placebo controlled food challenge (DBPCFC) or open OFC** for subjects with Sustained Unresponsiveness (SU) and Desensitisation (DS) without SU;
• Double blind, placebo controlled food challenge (DBPCFC) or open OFC** for subjects with
allergy if SPT <8mm and no recent immediate objective allergic reaction to peanut in the last 6 months;
• Spirometry as clinically indicated before each DBPCFC or OFC
A 2nd DBPCFC or OFC will be performed for DS without SU subjects if they pass the 1st F3 DBPCFC or OFC. These subjects will commence an 8-week period of peanut elimination after passing the first F3 DBPCFC or OFC, after which they will undergo a 2nd DBPCFC or OFC to assess for conversion to SU. The 2nd DBPCFC or OFC must be a minimum of 8 weeks post the 1st F3 challenge part A.
If the 1st DBPCFC or OFC is conducted more than 3 months after the F3 visit (for those who had the F3 visit prior to the protocol amendment (version 5), a repeat skin prick test and blood collection will be performed for the subject.
**The decision for DBPCFC or open OFC is at the discretion of the site investigator
The window for the F3 timepoint DBPCFC or OFC can be +/- 6 months (from 3.5 to 4.5 years post-treatment) to accommodate parent/participant availability.
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.

F4 time point (48 months after F0 or 60 months after the final day of treatment)
A visit will be conducted at this time point for the following:
• Weight/height;
• Skin prick test (peanut, egg, milk, cashew, almond, pistachio, hazelnut, dust mite and positive
and negative control);
• Blood and faecal sample (faecal sample collected by parents at home);
• Anaphylaxis education;
• Allergy questionnaire;
• Food Allergy Quality of Life-Parent Form (FAQL-PF), parental burden form (FAQL-PB) and age appropriate Food Allergy Quality of Life forms (i.e. participants aged 8-12 years and 13-17 years to complete Food Allergy Quality of Life-Child Form (FAQLQ-CF) and Food Allergy Quality of Life-Teenager Form (FAQLQ-TF) respectively);
• Medical history as clinically indicated prior to DBPCFC or OFC;
•Double blind, placebo controlled food challenge (DBPCFC) or open OFC** for all subjects (SU, DS without SU and allergic) – only if this was not performed at F3 with clinical outcome determined;
• Spirometry as clinically indicated before each DBPCFC or open OFC
A 2nd DBPCFC/OFC will be performed for DS without SU subjects if they pass the 1st F4 DBPCFC/OFC. These subjects will commence an 8-week period of peanut elimination after passing the 1st F4 DBPCFC/OFC, after which they will undergo a 2nd DBPCFC/OFC to assess for conversion to SU. The 2nd DBPCFC/OFC must be a minimum of 8 weeks post the 1st F4 DBPCFC part A or 1st F4 OFC. The procedures performed for the 2nd F4 DBPCFC/OFC will be similar to the 1st F4 DBPCFC/OFC (including repeat SPT, blood and stool sample collection and questionnaires).
If the DBPCFC/OFC is conducted more than 3 months after the F4 visit (for those who had the F4 visit prior to the protocol amendment (version 5 or earlier), a repeat skin prick test and blood collection will be performed for the subject.
**The decision for DBPCFC or open OFC is at the discretion of the site investigator
The window for the F4 timepoint DBPCFC/OFC can be +/- 6 months (from 4.5 to 5.5 years post-treatment) to accommodate parent/participant availability.
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.

***PPOIT-003 study participants who did not enrol in PPOIT-003LT will be invited back to complete a food challenge at the F4 timepoint. A PPOIT-003LT protocol ADDENDUM for participants who are currently not in the follow-on study and who will be invited for a long-term DBPCFC/OFC at the F4 timepoint (60 months post-treatment). These participants will not be required to complete a F5 visit.



F5 time point (60 months after F0 or 72 months after the final day of treatment)
A visit will be conducted at this time point for the following:
• Weight/height;
• Skin prick test (peanut, egg, milk, cashew, almond, pistachio, hazelnut, dust mite and positive and negative control);
• Blood and faecal sample (faecal sample collected by parents at home);
• Anaphylaxis education;
• Allergy questionnaire;
• Food Allergy Quality of Life-Parent Form (FAQL-PF), parental burden form (FAQL-PB), and age appropriate Food Allergy Quality of Life forms (i.e. participants aged 8-12 years and 13-17 years to complete Food Allergy Quality of Life-Child Form (FAQLQ-CF) and Food Allergy Quality of Life-Teenager Form (FAQLQ-TF) respectively);
• Spirometry (all children over 8 years)
As this is the final study visit, the window for the F5 time point can be +/- 6 months to accommodate parent/participant availability


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.

- This is the end point of the follow on study and participants will return to their Clinical Allergist for ongoing clinical care.
Intervention code [1] 314643 0
Not applicable
Comparator / control treatment
Active control (peanut avoidance) with no treatment given,
Control group
Active

Outcomes
Primary outcome [1] 320281 0
Proportion of subjects who are ingesting peanut in their diet and number and severity of reactions to peanut ingestion (intentional or accidental) during the follow-on study phase in PPOIT, OIT and placebo groups as well as in subjects with Sustained Unresponsiveness (SU) vs Desensitisation (DS) without SU vs allergic status.
This will be assessed using allergy questionnaires, quality of life forms and a study diary (in the form of a mobile app or paper).
Timepoint [1] 320281 0
F1 visit - 24 months post PPOIT 003 T1 visit (ACTRN12616000322437)
F2 visit - 36 months post PPOIT 003 T1 visit (ACTRN12616000322437)
F3 visit - 48 months post PPOIT 003 T1 visit (ACTRN12616000322437)
F4 visit - 60months post PPOIT 003 T1 visit (ACTRN12616000322437)
F5 visit - 72 months post PPOIT 003 T1 visit (ACTRN12616000322437)
Secondary outcome [1] 371127 0
Quality of life scores and change in quality of life scores from baseline in PPOIT-003 study at 24 months (F1), 36 months (F2), 48 months (F3), 60 months (F4) and 72 months (F5) post-treatment in PPOIT, OIT and placebo groups as well as in subjects with sustained unresponsiveness (SU) vs Desensitisation (DS) without SU vs allergic status (determined at end of treatment in PPOIT-003 study). This will be assessed using quality of life forms
Timepoint [1] 371127 0
F1 visit - 24 months post PPOIT 003 T1 visit (ACTRN12616000322437) F2 visit - 36 months post PPOIT 003 T1 visit (ACTRN12616000322437) F3 visit - 48 months post PPOIT 003 T1 visit (ACTRN12616000322437) F4 visit - 60 months post PPOIT-003 T1 visit (ACTRN12616000322437) F5 visit - 72 months post PPOIT-003 T1 visit. (ACTRN12616000322437)
Secondary outcome [2] 371130 0
Changes from PPOIT-003 study baseline in peanut and peanut component sIgE and sIgG4
levels and peanut skin prick test (SPT) at 36 months (F2), 48 months (F3), 60 months (F4) and
72 months (F5) post-treatment in PPOIT vs OIT vs placebo groups and in subjects with SU vs
DS without SU vs allergic status. This a composite secondary outcome. sIgE levels and sIgG4 levels will be assessed using plasma samples and measured by ImmunoCAP (Phadia).
Timepoint [2] 371130 0
F2 visit - 36 months post PPOIT 003 T1 visit (ACTRN12616000322437)
F3 visit - 48 months post PPOIT 003 T1 visit (ACTRN12616000322437)
F4 visit - 60 months post PPOIT-003 T1 visit (ACTRN12616000322437)
F5 visit - 72 months post PPOIT-003 T1 visit. (ACTRN12616000322437)
Secondary outcome [3] 414683 0
Measure of participants with persistent SU between 48 months (F3) and 60 months (F4) post-treatment amongst subjects who achieved SU at end of treatment in PPOIT vs OIT vs placebo groups. This will be assessed by performing a food challenge at F3 or F4.
Timepoint [3] 414683 0
F3 visit - 48 months post PPOIT 003 T1 visit (ACTRN12616000322437)
F4 visit - 60 months post PPOIT-003 T1 visit (ACTRN12616000322437)
Secondary outcome [4] 414684 0
Measure of participants with persistent DS without SU between 48 months (F3) and 60 months (F4) post-treatment amongst subjects who achieved persistent DS without SU at end of treatment in PPOIT vs OIT vs placebo groups. This will be assessed by performing a food challenge at F3 or F4.
Timepoint [4] 414684 0
F3 visit - 48 months post PPOIT 003 T1 visit (ACTRN12616000322437)
F4 visit - 60 months post PPOIT-003 T1 visit (ACTRN12616000322437)
Secondary outcome [5] 414685 0
Measure of participants who converted to SU between at 48 months (F3) and 60 months (F4) post-treatment amongst subjects who achieved persistent DS without SU at end of treatment in PPOIT vs OIT vs placebo groups. This will be assessed by performing a food challenge at F3 or F4.
Timepoint [5] 414685 0
F3 visit - 48 months post PPOIT 003 T1 visit (ACTRN12616000322437)
F4 visit - 60 months post PPOIT-003 T1 visit (ACTRN12616000322437)
Secondary outcome [6] 414686 0
Measure of participants with persistent SU between 48 months (F3) and 60 months (F4) post-treatment in PPOIT vs OIT vs placebo groups. This will be assessed by performing a food challenge at F3 or F4
Timepoint [6] 414686 0
F3 visit - 48 months post PPOIT 003 T1 visit (ACTRN12616000322437)
F4 visit - 60 months post PPOIT-003 T1 visit (ACTRN12616000322437)
Secondary outcome [7] 414687 0
Measure of participants with persistent DS without SU between 48 months (F3) and 60 months (F4) post-treatment in PPOIT vs OIT vs placebo groups. This will be assessed by performing a food challenge at F3 or F4.
Timepoint [7] 414687 0
F3 visit - 48 months post PPOIT 003 T1 visit (ACTRN12616000322437)
F4 visit - 60 months post PPOIT-003 T1 visit (ACTRN12616000322437)
Secondary outcome [8] 414688 0
Quality of life scores and change from baseline in quality of life scores in PPOIT-003 study between 48 months (F3) and 60 months (F4) post-treatment in subjects with persistent SU vs lost SU vs persistent DS vs converted SU vs allergic. This will be assessed using validated Food Allergy Quality of Life (FAQL) forms. This a composite secondary outcome.
Timepoint [8] 414688 0
F3 visit - 48 months post PPOIT 003 T1 visit (ACTRN12616000322437)
F4 visit - 60 months post PPOIT-003 T1 visit (ACTRN12616000322437)

Eligibility
Key inclusion criteria
Completion of the PPOIT-003 T2 visit according to PPOIT-003 protocol.
Enrolment into the PPOIT-003 study.
Minimum age
3 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Did not complete the PPOIT-003 T2 visit
Currently taking probiotic supplements (does not include formula, yoghurts and fermented foods).

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Both
Statistical methods / analysis
PPOIT-003LT will be analysed according to the intention-to-treat (ITT) principle. Subjects will be compared according to the group to which they were originally randomly allocated, regardless of subjects' compliance, crossover to other treatments or withdrawal from the follow-on study.

Additional analyses on safety will be conducted comparing subjects by their outcome at T2 of PPOIT-003 – SU vs desensitisation vs allergic.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
5/06/2019
Date of last participant enrolment
Anticipated
30/09/2020
Actual
21/09/2020
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
171
Accrual to date
Final
151
Recruitment in Australia
Recruitment state(s)
SA,WA,VIC
Recruitment hospital [1] 13894 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 13895 0
Perth Children's Hospital - Nedlands
Recruitment hospital [3] 13896 0
Womens and Childrens Hospital - North Adelaide
Recruitment postcode(s) [1] 26667 0
3052 - Parkville
Recruitment postcode(s) [2] 26668 0
6009 - Nedlands
Recruitment postcode(s) [3] 26669 0
5006 - North Adelaide

Funding & Sponsors
Funding source category [1] 302939 0
Commercial sector/Industry
Name [1] 302939 0
Prota Therapeutics
Country [1] 302939 0
Australia
Primary sponsor type
Other
Name
Murdoch Children's Research Institute
Address
The Royal Children's Hospital, 50 Flemington Road, Parkville 3052
Country
Australia
Secondary sponsor category [1] 303062 0
None
Name [1] 303062 0
Address [1] 303062 0
Country [1] 303062 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303501 0
Royal Children’s Hospital (RCH) Human Research Ethics Committee (HREC)
Ethics committee address [1] 303501 0
Ethics committee country [1] 303501 0
Australia
Date submitted for ethics approval [1] 303501 0
11/03/2019
Approval date [1] 303501 0
18/04/2019
Ethics approval number [1] 303501 0
2019.026

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93882 0
Dr Paxton Loke
Address 93882 0
Murdoch Children's Research Institute
Royal Children's Hospital
50 Flemington Road
Parkville 3052
Country 93882 0
Australia
Phone 93882 0
+61 422764232
Fax 93882 0
+61 3 9345 4848
Email 93882 0
paxton.loke@mcri.edu.au
Contact person for public queries
Name 93883 0
Julie Burns
Address 93883 0
Allergy Immunology Group
Murdoch Children's Research Institute
Royal Children's Hospital
50 Flemington Road
Parkville 3052
Country 93883 0
Australia
Phone 93883 0
+61 3 9936 6184
Fax 93883 0
+61 3 9345 4848
Email 93883 0
julie.burns@mcri.edu.au
Contact person for scientific queries
Name 93884 0
Julie Burns
Address 93884 0
Allergy Immunology Group
Murdoch Children's Research Institute
Royal Children's Hospital
50 Flemington Road
Parkville 3052
Country 93884 0
Australia
Phone 93884 0
+61 3 9936 6184
Fax 93884 0
+61 3 9345 4848
Email 93884 0
julie.burns@mcri.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The study protocol, documentation, data and all other information generated will be held in strict confidence. No information concerning the study or the data will be released to any unauthorised third party, without prior written approval of the sponsoring institution.

Authorised representatives of the sponsoring institution may inspect all documents and records required to be maintained by the Site Investigator, including but not limited to, medical records (office, clinic or hospital) and pharmacy records for the participants in this study.

All laboratory specimens, evaluation forms, reports and other records that leave the site will be identified only by the Participant Identification Number (SID) to maintain participant confidentiality. Clinical information will not be released without written permission of the participant, except as necessary for monitoring by HREC or regulatory agencies.


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
No additional documents have been identified.