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Trial registered on ANZCTR


Registration number
ACTRN12616000977471
Ethics application status
Approved
Date submitted
19/07/2016
Date registered
25/07/2016
Date last updated
25/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical trial in children presenting to hospital with an asthma attack, to compare the effectiveness of giving the additional treatment of anti-immunoglobulin E antibody or nothing on the time until their next asthma attack.
Scientific title
A double-blind, randomized, placebo-controlled study evaluating the efficacy of anti-IgE antibody, omalizumab, for the prevention of subsequent asthma exacerbations in children aged 6-12 years (OMALIZ612)
Secondary ID [1] 287641 0
CIGE025B2401T
Universal Trial Number (UTN)
U1111-1175-4795
Trial acronym
OMALIZ612
Linked study record

Health condition
Health condition(s) or problem(s) studied:
asthma exacerbations 296463 0
Condition category
Condition code
Respiratory 296721 296721 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
anti-IgE antibody, omalizumab.
The dose of omalizumab to be administered to each subject will be calculated using the subject’s baseline total serum or plasma IgE levels (IU/ml) plus the subject’s weight (kg) in accordance with the dosing table (described in the Xolair (Registered Trademark) (Omalizumab) Product Information Sheet). The Product Information Sheet is listed under Xolair (Registered Trademark) on the the Health Care Professionals page in the following website
https://www.novartis.com.au/products/healthcare-professionals
The dose will be given as a subcutaneous (SC) injection.
A single dose of omalizumab will be given. However, in accordance with the dosing table, each participant with sufficient body weight (kg) and total IgE levels to require a second dose of Omalizumab, will need their second dose of either Omalizumab or placebo to be given two weeks later.
The treatment drug, omalizumab, (or placebo) will be administered at least 12 hours after the patient presents to hospital, at the enrolment visit.
Treatment will be given in the hospital, so adherence will be monitored by the person administering the treatment
Intervention code [1] 293039 0
Treatment: Drugs
Comparator / control treatment
Normal saline (0.9% w/v)
Control group
Placebo

Outcomes
Primary outcome [1] 296342 0
Time (number of days) to next asthma exacerbation in the subsequent six months
This will be assessed by the review of medical records and diary records completed by the parents.
Timepoint [1] 296342 0
Six months post recruitment at presentation to hospital with an asthma exacerbation
Secondary outcome [1] 318213 0
Time (number of days or hours) to discharge
This will be assessed by the review of medical records.
Timepoint [1] 318213 0
Date and time of discharge
Secondary outcome [2] 325424 0
Amount (number of doses) of short-acting beta2 agonists required in the first 6, 12 and 24 hours after treatment with omalizumab
This will be assessed by the review of medical records.
Timepoint [2] 325424 0
6, 12 and 24 hours after treatment with omalizumab
Secondary outcome [3] 325425 0
Time (number of days) respiratory symptoms persist after asthma exacerbation
This will be assessed by the review of diary records completed by the parents.
Timepoint [3] 325425 0
Date of end of respiratory symptoms following recruitment asthma exacerbation
Secondary outcome [4] 325426 0
Amount (number) of asthma exacerbations in subsequent 6 months
This will be assessed by the review of medical records and diary records completed by the parents.
Timepoint [4] 325426 0
6 months following recruitment asthma exacerbation
Secondary outcome [5] 325850 0
Amount (number) of asthma exacerbations in subsequent 12 months
This will be assessed by the review of medical records and diary records completed by the parents as well as telephone interview at 12 months post recruitment.
Timepoint [5] 325850 0
Twelve months post recruitment at presentation to hospital with an asthma exacerbation.

Eligibility
Key inclusion criteria
1. Male or female children 6-12 years of age presenting to PMH ED with a diagnosis of either acute asthma or asthma exacerbation by the treating physician.
2. An acute asthma severity score of moderate or severe as defined by Qureshi, F. et al. NEJM (1998) 339:1030-5.
3. Admission to hospital with acute wheeze or asthma at least once in the previous year.
4. Parent(s) or legal guardian(s) of the child is able to understand the study requirements and willing to provide informed consent
Minimum age
6 Years
Maximum age
12 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
A child who meets any of the following criteria will be excluded from the study:
1. Known (or evidence of) chronic underlying condition (other than asthma)
2. Known hypersensitivity to omalizumab or other anti-IgE drugs
3. History of a previous doctor diagnosis of anaphylaxis
4. At high risk of chronic helminth infection
5. History of malignancy
6. History of a prior diagnosis with cardiovascular disease or an arterial thromboembolic event
7. Treatment with immunosuppressant drugs including methotrexate, cyclosporine or azathioprine within 30 days prior to enrolment in this study
8. Treatment with omalizumab within 6 months prior to enrolment in this study
9. Participation in another randomized control trial within the 3 months preceding enrolment in this study
10. Any clinically relevant abnormal findings in physical examination and/or vital signs at Visit 1, which, in the opinion of the investigator, may deem the child unsuitable for the study.
11. Pregnancy, breast-feeding or planned pregnancy during the study. Female participants who are fertile (i.e. have reached menarche) will undergo a pregnancy test by urine dipstick.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
We use an electronic tool from a website called Randomisation.com to generate the sequence.
Allocation involved contacting the holder of the allocation schedule who is independent of the recruitment team and will prepare the treatment or placebo.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
(link: http://www.randomization.com/
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Type of endpoint/s
Efficacy
Statistical methods / analysis
We will analyse the data using an intention-to-treat analysis strategy to compare the difference in asthma severity scores, treatment response outcomes, length of stay in hospital, time to resolution of symptoms and subsequent exacerbation rates between the intervention and placebo groups. Analysis of variance or independent sample T tests, where appropriate will be employed for the comparison of the outcome variables with a normal or transformed normal distribution. For the data with a non-normal distribution, corresponding non-parametric tests will be used. As we will follow up the clinical trial cohort up to 12 months, we will employ survival and Poisson analysis methods to investigate the effects of the intervention on the outcome variables: time to event and number of recurrent infections, respectively.
We assume 80% will complete the follow-up as this is expected based on our experience in other clinical research trials and research studies.  Thus, we need to recruit at least 128 subjects. We have now also calculated the power with the primary objectives of time to recurrence of asthma symptoms (exacerbation). A two-sided logrank test with an overall final sample size of 100 subjects (50 in the control group and 50 in the treatment group) achieves 79.3% power at a 0.050 significance level to detect a hazard ratio of 0.5 when the control group hazard rate is a hazard ratio of 1.00.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2016
Actual
Date of last participant enrolment
Anticipated
1/10/2019
Actual
Date of last data collection
Anticipated
1/10/2021
Actual
Sample size
Target
128
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 4943 0
Princess Margaret Hospital - Subiaco
Recruitment postcode(s) [1] 12451 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 292558 0
Government body
Name [1] 292558 0
National Health and Medical Research Council
Country [1] 292558 0
Australia
Funding source category [2] 294018 0
Commercial sector/Industry
Name [2] 294018 0
Novartis
Country [2] 294018 0
Australia
Primary sponsor type
University
Name
The University of Western Australia
Address
35 Stirling Highway
Perth WA 6009
Australia
Country
Australia
Secondary sponsor category [1] 291278 0
None
Name [1] 291278 0
Address [1] 291278 0
Country [1] 291278 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294034 0
Princess Margaret Hospital for Children Human Ethics Committee
Ethics committee address [1] 294034 0
Level 1, Children's Clinical Research Facility
Princess Margaret Hospital
Roberts Road, Subiaco WA 6008
GPO Box D184
Perth WA 6840
Ethics committee country [1] 294034 0
Australia
Date submitted for ethics approval [1] 294034 0
18/08/2015
Approval date [1] 294034 0
01/12/2015
Ethics approval number [1] 294034 0
2015182

Summary
Brief summary
Double-blind, randomized, placebo-controlled, clinical trial with the primary objective to determine the efficacy of omalizumab given to children aged 6-12 years during an acute asthma exacerbation to prevent asthma exacerbations in the subsequent six months.
Subjects include male and female children aged 6-12 years presenting to Princess Margaret Hospital for Children (PMH) Emergency Department with moderate to severe acute asthma. The ‘treatment’ group (n=64) will receive one dose of omalizumab at the enrolment visit (Visit 1). The ‘placebo’ group (n=64) will receive one dose of a placebo at the enrolment visit (Visit 1). However, in accordance with the dosing table (described in the Xolair (Registered Trademark) (Omalizumab) Product Information Sheet), each participant with sufficient body weight (kg) and total IgE levels to require a second dose of Omalizumab, will need to have a second dose of either Omalizumab or placebo two weeks later. The treatment drug, omalizumab, (or placebo) will be administered at least 12 hours after the patient presents to hospital, at the enrolment visit and following treatment, the patient will be monitored for a minimum of two hours by an experienced paediatrician. All children will also receive standard asthma therapy according to the PMH Clinical Practice Guidelines. This study consists of 3-4 visits over six months (including the first enrolment and treatment visit) and 1 follow-up telephone interview at 12 months.
Trial website
Trial related presentations / publications
Public notes
This is a proof of concept clinical trial

Contacts
Principal investigator
Name 60918 0
Prof Peter Le Souef
Address 60918 0
Professor of Paediatrics
Consultant Respiratory Physician
School of Paediatrics and Child Health, The University of Western Australia and Princess Margaret Hospital for Children
GPO Box D184, Perth, WA, AUSTRALIA 6840
Country 60918 0
Australia
Phone 60918 0
+61893408173
Fax 60918 0
+61893882097
Email 60918 0
[email protected]
Contact person for public queries
Name 60919 0
Ingrid Laing
Address 60919 0
Senior Research Fellow
UWA SPACH Children's Respiratory Research Group
Telethon Kids Institute
PO Box 855 West Perth WA 6872
Country 60919 0
Australia
Phone 60919 0
+61894897706
Fax 60919 0
+61894897700
Email 60919 0
[email protected]
Contact person for scientific queries
Name 60920 0
Ingrid Laing
Address 60920 0
Senior Research Fellow
UWA SPACH Respiratory Research Group
Telethon Kids Institute
PO Box 855 West Perth WA 6872
Country 60920 0
Australia
Phone 60920 0
+61894897706
Fax 60920 0
+61894897700
Email 60920 0
[email protected]

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