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Trial registered on ANZCTR


Registration number
ACTRN12620001203943
Ethics application status
Approved
Date submitted
16/09/2020
Date registered
12/11/2020
Date last updated
12/11/2020
Date data sharing statement initially provided
12/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
OPAL: Combining Peanut Oral Immunotherapy and Omalizumab in Adults with Peanut Allergy
Scientific title
Assessing the Utility of Combining Peanut Oral Immunotherapy and Omalizumab in Adults In Improving Tolerance of Peanut Protein with Peanut Allergy
Secondary ID [1] 302270 0
Nil
Universal Trial Number (UTN)
Trial acronym
OPAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peanut allergy 318996 0
Condition category
Condition code
Inflammatory and Immune System 316964 316964 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Phase 1: Week 0 to 11 (inclusive)- Omalizumab only:
Subcutaneous injection of 300mg omalizumab will occur on Weeks 0 (baseline), 4, 8, 12, 16 and 20.
Injection will be administered by the study nurse into the upper arms of the participant, and all participants will be observed for a minimum of 30 minutes following administration of the dose.

Phase 2: Week 12 to 24 (inclusive)- Omalizumab and Induction Immunotherapy:
Oral immunotherapy will be administered from Week 12 through to Week 48. Weeks 12 to 24 is induction immunotherapy. Weeks 24 to 48 is maintenance immunotherapy.
Immunotherapy will be initiated on Day 1 of Week 12. Day 1 will consist of multiple steps of building up to a dose of 25mg peanut protein (Rush Induction). Dosing will be administered in the form of roasted peanut fines or peanut flour. Rush induction will be performed in a clinical setting at the study site, and doses of peanut protein will be administered by the study nurse.
If the participant tolerates all doses, they will be observed for a minimum of 2 hours prior to discharge and return on Day 2 for a single administration of 25mg of peanut protein under the same conditions as Day 1. If tolerated, participants will be given with individual packages of daily 25mg peanut protein doses to take at the home for the next fortnight. They will also be given an Immunotherapy Diary to be completed daily, marking the date and time the immunotherapy was taken, and any reactions experienced.
At the end of this fortnight, participants will return to clinic to receive an increased dose of peanut protein. This dose of peanut protein will be administered by the study nurse. If tolerated the participant will be sent home with a 14-day supply of the new dose of immunotherapy.
Doses will continue to be increased fortnightly as follows:
Weeks 12-13: 25mg
Weeks 14-15: 50mg
Weeks 16-17: 100mg
Weeks 18-19: 150mg
Weeks 20 -21: 150mg (new peanut product)
Weeks 22-23: 200mg
At Week 20 there will be no increase in dose, but participants will be changed from peanut flour to their choice of either whole roasted peanut or smooth peanut butter of equivalent peanut content (e.g. ½ a peanut kernel or 0.3g peanut butter). The first dose will be supervised as per previous up-dosing, and if tolerated they will be required to take the same amount of that peanut product daily for 2 weeks. All subsequent immunotherapy will be given in this same form.
Immunotherapy diaries will be checked at each of these study visits.
Omalizumab will continue to be given every 4 weeks during this time, with the final dose of omalizumab given at Week 20

Phase 3: Week 24 to end of study (Week 48)- Maintenance Immunotherapy:
Participants will be continued on a daily dose of 300mg peanut protein in the form of patient’s preference.
Intervention code [1] 318556 0
Treatment: Drugs
Intervention code [2] 318557 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 325070 0
Maximum tolerated dose of peanut at Week 48 double-blind, placebo-controlled food challenge
Timepoint [1] 325070 0
Week 48
Secondary outcome [1] 386729 0
Differences in maximum tolerated peanut protein between baseline, Week 24 and Week 48 as assessed by the maximum tolerated dose of peanut protein at double-blind, placebo-controlled food challenges at these time points
Timepoint [1] 386729 0
Baseline, Weeks 24 and 48
Secondary outcome [2] 386732 0
Changes in total and specific responses in serum IgE, IgG4 and basophil reactivity in response to study interventions when compared to baseline
Timepoint [2] 386732 0
Screening, Weeks 12, 24 and 48
Secondary outcome [3] 386733 0
Changes in food allergy-associated quality of life parameters in participants when compared to baseline as assessed by the Food Allergy Quality of Life Questionnaire- Adult Form, and the Food Allergy Independent Measure
Timepoint [3] 386733 0
Screening, Weeks 24 and 48
Secondary outcome [4] 386734 0
Safety of peanut oral immunotherapy as indicated by adverse reactions attributable to peanut oral immunotherapy. This will assessed by severity and number of reactions documented by the participants in their Immunotherapy Diary
Timepoint [4] 386734 0
Adverse reactions to peanut immunotherapy will be assessed at all study visits from Week 12 Day 2 to Week 48 (total of 11 visits)

Eligibility
Key inclusion criteria
- Age greater than or equal to 16 years
- History of immediate (Type 1) allergic reaction to peanut
- Positive response to less than 300mg of peanut protein at the screening double-blind, placebo-controlled oral peanut challenge
- Skin prick test to peanut reagent greater than 3mm with appropriate responses to positive and negative controls
- Willing and able to give written informed consent to participate in and comply with all aspects of the study
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Anaphylaxis to peanut requiring intensive care unit admission in the previous 5 years
- Participants who react to placebo at double-blind, placebo-controlled challenge
- Women who are lactating, pregnant or of childbearing potential and not willing to avoid becoming pregnant during the study
- Severe or unstable asthma
- Unstable cardiac disease
- Ongoing treatment with a beta-blocker, angiotensin converting enzyme inhibitor, calcium channel blocker, angiotensin receptor blocker or non-steroidal anti-inflammatory drug
- Participants that cannot be safely taken off oral corticosteroid therapy for 7 days or antihistamines for 72 hours for the purposes of oral peanut challenge
- Prior peanut immunotherapy
- Omalizumab or mepolizumab in the previous 3 months
- Other medical condition that the investigator considers will unacceptably increase the risk of peanut oral challenge

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
To achieve improved peanut tolerance from 30-40% seen in previous studies with peanut immunotherapy alone to 80% with omalizumab, 25 participants are needed for recruitment (alpha 0.05, power 0.8, 25% loss to follow up)
Primary outcomes will be analysed by intention-to-treat, and described as proportions of the study population who achieve the target outcomes.
Secondary outcomes will be assessed using t-tests.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 17463 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 17464 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [3] 17465 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 17466 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [5] 17467 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 31195 0
2148 - Blacktown
Recruitment postcode(s) [2] 31196 0
2560 - Campbelltown
Recruitment postcode(s) [3] 31197 0
2170 - Liverpool
Recruitment postcode(s) [4] 31198 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 31199 0
2145 - Westmead
Recruitment postcode(s) [6] 31200 0
2085 - Belrose

Funding & Sponsors
Funding source category [1] 306689 0
Other Collaborative groups
Name [1] 306689 0
SPHERE Triple I
Address [1] 306689 0
Level 4
Lowy Building
UNSW
SYDNEY NSW 2052
Country [1] 306689 0
Australia
Funding source category [2] 306691 0
Charities/Societies/Foundations
Name [2] 306691 0
Balnaves Foundation
Address [2] 306691 0
Suite 2 Level 8
139 Macquarie St,
Sydney NSW 2000
Country [2] 306691 0
Australia
Funding source category [3] 306692 0
Charities/Societies/Foundations
Name [3] 306692 0
St Vincent's Curran Fondation
Address [3] 306692 0
Fundraising Office
Level 3, de Lacy Building
St Vincent’s Hospital
390 Victoria Street
Darlinghurst NSW 2010
Country [3] 306692 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Sydney
Address
390 Victoria St
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 307241 0
None
Name [1] 307241 0
Nil
Address [1] 307241 0
NA
Country [1] 307241 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306866 0
South Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 306866 0
Locked Bag 7103
Liverpool BC NSW 1871
Ethics committee country [1] 306866 0
Australia
Date submitted for ethics approval [1] 306866 0
Approval date [1] 306866 0
29/01/2020
Ethics approval number [1] 306866 0
2019/ETH13494

Summary
Brief summary
This is a prospective, single-arm study of adults who react at blinded challenge to less than 300mg of peanut protein (approx. one peanut kernel) that will evaluate the utility of omalizumab as an adjunctive therapy to improve safety, as indicated by severity and frequency of reactions due to immunotherapy, and patient acceptability, as indicated by improved completion of the full course of oral immunotherapy, when compared to existing literature.
Treatment in the study will consist of three phases. For the first phase, all participants will receive omalizumab injections every 4 weeks for 12 weeks. In the second 12 weeks, all participants will commence peanut oral immunotherapy and will continue omalizumab injections every 4 weeks. In the third phase, from week 24, omalizumab will cease and a maintenance dose of peanut will continue until the final study visit at 48 weeks.
DBPCFC will be performed at screening, Week 24 and Week 48.
Peanut protein doses of up to 100mg will be in the form of roast peanut fines or flour. Doses of 150mg and above will be taken in the form of whole roast peanut or smooth peanut butter according to patient preference.
At Baseline, Week 12, Week 24 and Week 48 blood will be collected and tested for specific IgE, IgG4 and basophil activation tests to total peanut protein and protein components to assess for changes in peanut-specific immunity in response to trial interventions, and to evaluate the utility of such tests in predicting outcomes to therapy in adults
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105286 0
Prof Andrew Carr
Address 105286 0
St Vincent's Hospital Sydney
390 Victoria St
Darlinghurst NSW 2010
Country 105286 0
Australia
Phone 105286 0
+61 2 83823359
Fax 105286 0
Email 105286 0
andrew.carr@svha.org.au
Contact person for public queries
Name 105287 0
Dr Jacqueline Loprete
Address 105287 0
St Vincent's Hospital Sydney
390 Victoria St
Darlinghurst NSW 2010
Country 105287 0
Australia
Phone 105287 0
+61436949244
Fax 105287 0
Email 105287 0
jacqueline.loprete@svha.org.au
Contact person for scientific queries
Name 105288 0
Dr Jacqueline Loprete
Address 105288 0
St Vincent's Hospital Sydney
390 Victoria St
Darlinghurst NSW 2010
Country 105288 0
Australia
Phone 105288 0
+61 2 83823797
Fax 105288 0
Email 105288 0
jacqueline.loprete@svha.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results