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Trial registered on ANZCTR


Registration number
ACTRN12619000306112
Ethics application status
Approved
Date submitted
11/12/2018
Date registered
28/02/2019
Date last updated
8/11/2022
Date data sharing statement initially provided
28/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
An Open-label Study of Probiotic and Hen’s Egg or Cow’s Milk Oral Immunotherapy (Probiotic and Egg or Milk Oral Immunotherapy: PrEMO study).
Scientific title
An Open-label Study of Probiotic and Hen’s Egg or Cow’s Milk Oral Immunotherapy (Probiotic and Egg or Milk Oral Immunotherapy: PrEMO study). Children aged 5 to 17 years with either an egg allergy and/or milk allergy will be recruited.
Secondary ID [1] 296833 0
none
Universal Trial Number (UTN)
U1111-1225-2896
Trial acronym
Probiotic and Egg or Milk Oral Immunotherapy: PrEMO study
Linked study record
no linked study

Health condition
Health condition(s) or problem(s) studied:
hens egg allergy
 310735 0
cows milk allergy 310736 0
Condition category
Condition code
Inflammatory and Immune System 309426 309426 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Probiotic and Egg or Milk Oral Immunotherapy: PrEMO study
Egg or milk allergic participants
Participants will commence the study on the RUSH day (rapid updosing schedule day) where increasing doses of egg white powder or milk powder are given (commencing at 0.4 mg and 0.51 mg respectively) along with a single dose of L. rhamnosus strain probiotic. Each participant will be put on a dose for a period of 2 weeks. If the participant reacts to a dose, they will go home on the previous dose. For example, if they react to dose 4, they will go home on dose 3, commencing the following day for a period of two weeks. The balance of the RUSH doses will be incorporated into their build up schedule.
All participants (regardless of what dose they went home on RUSH day) will continue to come back every two weeks for up-dosing in hospital until the maintenance dose is reached (2000 mg and 3400 mg respectively). Once the maintenance dose is reached, they will come in every three months for a review of treatment until a total of 18 months is complete. The probiotic will be taken as a single daily dose for the duration of the 18 months.
Once the 18 months of treatment has been completed, participants will stop taking the study product for 8 weeks, after which they will undergo double-blind placebo-controlled food challenges (DBPCFC) to either egg or milk. First dose of the challenge will be 30mg for egg and 3.4mg for milk, with top doses being 2400mg for egg and 3400mg for milk. Egg white or milk powder will be used to challenge on the active day and a rice flour placebo will be used on the placebo day. This is to determine whether participants remain as "allergic" or has achieved "sustained unresponsiveness".
There will be a safety follow up phone call 12 months after treatment completion.
Intervention code [1] 313118 0
Treatment: Other
Comparator / control treatment
There will be a placebo component to the food challenges only. It will be a double blind placebo controlled food challenge. The placebo will be made of rice flour and food colouring to mimic the taste and appearance of egg white powder or milk powder.
Control group
Active

Outcomes
Primary outcome [1] 308384 0
To determine the proportion of children who can complete the dose-escalation (rush and build-up phase) according to the protocol. This will be measured by looking at how many participants were able to complete the RUSH and build up phase without reactions or delays.
Timepoint [1] 308384 0
Last day of build up phase = T1.
Secondary outcome [1] 354819 0
To evaluate adverse events (AE) during the dose-escalation phase and maintenance phase. For example allergic reactions to study product. Study doctors will assess and categorise as we are notified of them.
Timepoint [1] 354819 0
End of Maintenance phase =T2.
Secondary outcome [2] 354821 0
To determine the proportion of children who attain sustained unresponsiveness at end-of-treatment, defined as passing a DBPCFC 8 weeks post-treatment (T3) with strict avoidance of egg or milk intake between T2 and T3. Any egg or milk intake will be captured in a questionnaire administered at T3.
Participants will have passed if they did not have any reactions meeting the stopping criteria for DBPCFC.
Timepoint [2] 354821 0
T3, 8 weeks after T2
Secondary outcome [3] 354822 0
To determine the change from baseline in skin prick test wheal size at T1 and T3. Wheal size will be measured with a ruler by a person independent to the study who is trained in measuring SPT.
Timepoint [3] 354822 0
T3
Secondary outcome [4] 354823 0
To determine the change from baseline in immunological measures (sIgE and sIgG4) at T1 and T3. This will be a composite outcome using the blood samples provided.
Timepoint [4] 354823 0
T3
Secondary outcome [5] 354824 0
To assess change in quality of life from baseline to end of treatment and 12-month post treatment using the validated Food Allergy Quality of Life Questionnaire (FAQLQ).
Timepoint [5] 354824 0
T3 (8-weeks post-end-of-treatment) and T4 (12-month post treatment).

Eligibility
Key inclusion criteria
• Aged between 5 and 17 years of age
• Confirmed diagnosis of egg allergy or cow’s milk allergy as defined by a failed DBPCFC and a positive SPT or sIgE to egg or cow’s milk at screening
• Participants who are on an egg or milk elimination diet (baked egg or baked milk ingestion is allowed)
Minimum age
5 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Subjects who are on an egg or milk ladder diet (except baked egg or baked milk)
• 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 of less than 85% predicted at rest and FEV1/FVC of less than or equal to 85% predicted at rest 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
• History of eosinophilic oesophagitis (EoE)
• 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 within the past 6 months
• Reacting to the placebo component during the study entry DBPCFC
• Currently receiving or 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
• 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
n/a
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Participants will be allocated to egg or milk depending on what they are allergic to. If they are allergic to both egg and milk, the families can decide which allergen they would prefer to be allocated to. They can also delegate the decision to the study team if they wish, where the study doctor will make a decision based on the participant's medical history.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
No formal statistical analyses will be performed

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/03/2019
Actual
18/03/2019
Date of last participant enrolment
Anticipated
12/08/2019
Actual
23/09/2019
Date of last data collection
Anticipated
31/05/2022
Actual
31/05/2022
Sample size
Target
40
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12694 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 25116 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 301408 0
Commercial sector/Industry
Name [1] 301408 0
Prota Therapeutics
Country [1] 301408 0
Australia
Primary sponsor type
Other
Name
Murdoch Children's Research Institute
Address
50 Flemington Road
Parkville, Victoria, 3052
Country
Australia
Secondary sponsor category [1] 301092 0
None
Name [1] 301092 0
none
Address [1] 301092 0
none
Country [1] 301092 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302143 0
Royal Children's Hospital
Ethics committee address [1] 302143 0
Ethics committee country [1] 302143 0
Australia
Date submitted for ethics approval [1] 302143 0
14/11/2018
Approval date [1] 302143 0
22/01/2019
Ethics approval number [1] 302143 0

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

Contacts
Principal investigator
Name 89266 0
Dr Adriana Chebar Lozinsky Rolnik
Address 89266 0
Murdoch Children's Research Institute
50 Flemington Road,
Parkville, Victoria, 3052
Country 89266 0
Australia
Phone 89266 0
+61 393455911
Fax 89266 0
Email 89266 0
[email protected]
Contact person for public queries
Name 89267 0
Sigrid Pitkin
Address 89267 0
Murdoch Children's Research Institute
50 Flemington Road,
Parkville, Victoria, 3052
Country 89267 0
Australia
Phone 89267 0
+61 393456068
Fax 89267 0
Email 89267 0
[email protected]
Contact person for scientific queries
Name 89268 0
Mimi Tang
Address 89268 0
Murdoch Children's Research Institute
50 Flemington Road,
Parkville, Victoria, 3052
Country 89268 0
Australia
Phone 89268 0
+61 393455911
Fax 89268 0
Email 89268 0
[email protected]

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. 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.