Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000844640
Ethics application status
Approved
Date submitted
15/07/2023
Date registered
7/08/2023
Date last updated
7/08/2023
Date data sharing statement initially provided
7/08/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Australian Ustekinumab Real-world Observational Research - AURORA study
Scientific title
Australian multicentre, prospective observational cohort study to evaluate the real-world efficacy of ustekinumab in patients with moderate to severe Crohn's disease: AURORA study
Secondary ID [1] 310015 0
None
Universal Trial Number (UTN)
U1111-1294-4259
Trial acronym
AURORA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Inflammatory Bowel Disease 330519 0
Crohn's disease 330520 0
Condition category
Condition code
Oral and Gastrointestinal 327371 327371 0 0
Inflammatory bowel disease
Oral and Gastrointestinal 327372 327372 0 0
Crohn's disease
Inflammatory and Immune System 327373 327373 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The participants will be enrolled into this study since they are about to start ustekinumab therapy for Crohn's disease regardless of this study participation. As part of usual care, participants will receive a single weight-based ustekinumab IV induction dose at week 0 (260mg for weight equal or less than 55kg; 390mg for weight >55kg and equal or less than 85kg; 520mg for weight >85kg). At week 8, and every 8 weeks thereafter, participants will receive standard dosing of ustekinumab 90mg subcutaneous maintenance through to the end of study period. Patients who have an inadequate response can undergo dose escalation of ustekinumab by the study team as per standard care via compassionate dosing.

There will be six study visits, including the baseline visit, over 27 months’ follow-up period for participants who achieve and maintain clinical response to ustekinumab. All study visits will occur as per standard of care to conform to the Australian Pharmaceutical Benefits Scheme assessment criteria

At each study visit, participants will receive standard clinical care by their inflammatory bowel disease treatment team, which may include clinical assessment and standard local laboratory pathology tests. Additionally, the study team and the participants are required to complete questionnaires to assess secondary outcomes, and additional blood samples will be collected at each study visit to assess pharmacokinetics/ immunogenicity and pharmacodynamic markers associated with response to ustekinumab. This will add additional 15-30min to their usual clinic visits. The questionnaires will be administered by the investigators at each site which can include both doctors or research assistants who have been delegated to this projects. Participants also have the option to participate in a biospecimen sub-study (no restriction on how many can participate) during which additional stool samples will be collected at baseline, at 3 months and 27 months post enrolment and endoscopy biopsy samples will be collected at the time of endoscopic procedures (which could vary according to practice pattern at each site but it will be 1-2 endoscopic procedures within 27 months follow-up) to evaluate the cellular and molecular mechanisms of action of ustekinumab. The aim of the sub-study is to explain interindividual variability to response and help identify population subgroups that respond differently to standard ustekinumab therapy.

According to Australian standards of care, participants will be assessed by colonoscopy and/or intestinal imaging (CT/MRI or intestinal ultrasound) at baseline to confirm disease burden. There will be at least one colonoscopy between 9 and 15 months after enrolment to determine endoscopic response. This is considered a separate endoscopy visit. All intestinal imaging occurring during the study period will be documented and results recorded at each study visit.
Intervention code [1] 326435 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335237 0
To determine the proportion of patient with clinical remission from the completed questionnaires including CDAI/PRO2 and HBI
Timepoint [1] 335237 0
3 and 27 months post-enrolment
Secondary outcome [1] 423603 0
To determine the proportion of patients with clinical response from the completed questionnaires including CDAI/PRO2 and HBI
Timepoint [1] 423603 0
3 months post-enrolment
Secondary outcome [2] 423604 0
To determine the proportion of patients with sustained steroid-free response and remission (as a composite secondary outcome) from the completed questionnaires which were designed specifically for this study
Timepoint [2] 423604 0
15 and 27 months post-enrolment
Secondary outcome [3] 424243 0
To. determine ustekinumab treatment persistence from the completed questionnaires which were designed specifically for this study
Timepoint [3] 424243 0
15 and 27 months post-enrolment
Secondary outcome [4] 424244 0
To determine the proportion of patients requiring dose escalation from the completed questionnaires which were designed specifically for this study.
Timepoint [4] 424244 0
3, 9, 15, 21 and 27 months post-enrolment
Secondary outcome [5] 424245 0
To determine the effect of concomitant immunomodulator use in clinical remission from the completed questionnaires including CDAI/PRO2 and HBI
Timepoint [5] 424245 0
3, 9, 15, 21 and 27 months post-enrolment
Secondary outcome [6] 424246 0
To determine the proportion of patients with endoscopic response and remission (as a composite secondary outcome) in patients undergoing endoscopy during the study period from the colonoscopy reports.
Timepoint [6] 424246 0
15 and 27 months post-enrolment
Secondary outcome [7] 424247 0
To determine the proportion of patients with intestinal imaging improvement from baseline from intestinal ultrasound reports
Timepoint [7] 424247 0
3, 9, 15, 21 and 27 months post-enrolment
Secondary outcome [8] 424248 0
The proportion of participants undergoing endoscopy during the study period who exhibit any change in histology determined by histological assessment of intestinal biopsy.
Timepoint [8] 424248 0
15 and 27 months post-enrolment
Secondary outcome [9] 424249 0
To determine the effect of ustekinumab on composite quality of life measures from the completed questionnaires including SIBDQ, IBDDI and PROMIS-29
Timepoint [9] 424249 0
0, 3, 9, 15, 21 and 27 months post-enrolment
Secondary outcome [10] 424250 0
To determine the proportion of patients with postoperative recurrence in those who received ustekinumab post intestinal surgery for Crohn's disease from the completed questionnaires which were designed specifically for this study
Timepoint [10] 424250 0
27 months post-enrolment
Secondary outcome [11] 424251 0
To determine the proportion of patients with adverse events and serious adverse events from the completed questionnaires which were designed specifically for this study. Commonly reported adverse events included infections, injection site reactions, abdominal pain, nausea, arthralgia, and headache.
Timepoint [11] 424251 0
3, 9, 15,21 and 27 months post-enrolment
Secondary outcome [12] 424252 0
To determine the effect of ustekinumab on healthcare utilisation as reported by patients in completed questionnaires which were designed specifically for this study
Timepoint [12] 424252 0
15 and 27 months post-enrolment

Eligibility
Key inclusion criteria
Participants must be men and women aged between 18 and 80 at the time of informed consent with moderately to severely active Crohn’s disease of at least 3 months’ duration since diagnosis who are eligible for ustekinumab treatment through the Australian Pharmaceutical Benefit Scheme.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to provide informed consent

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Continuous variables will be analysed using descriptive summary statistics, including number of participants, mean, standard deviation, median and range. Categorical variables will be described with frequency counts and percentages. Pre-specified groups for statistical analysis include remitters, responders, and non-responders at the specified time points. p values for between group comparisons will be calculated from chi-square for categorical variables and t-tests for continuous variables with normal distribution and non-parametric testing for non-normally distributed data.

Kaplan-Meier survival analyses will be used to analyse individual predictors and display survival curves. Cox proportional hazards regression will be used to analyse multivariable survival data. Purposeful selection will be used to create a multivariable model by including variables from the univariate analysis with a p-value <0.10. Variables will then be excluded from this model that do not reach significance (p<0.05). Excluded variables will be added back to the model one at a time to check for confounding. Hazard ratios and 95% confidence intervals (CI) will be reported. Logistic regression, adjusting for relevant covariates will be used to define odds ratio’s (95% CI) to assess risk of disease flare during the period of the study and while participants are on ustekinumab treatment.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
31/05/2019
Date of last participant enrolment
Anticipated
Actual
2/08/2022
Date of last data collection
Anticipated
6/11/2024
Actual
Sample size
Target
200
Accrual to date
Final
197
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 25001 0
Mater Hospital Brisbane - South Brisbane
Recruitment hospital [2] 25002 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [3] 25003 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 25004 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [5] 25005 0
The Alfred - Melbourne
Recruitment hospital [6] 25006 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [7] 25007 0
Box Hill Hospital - Box Hill
Recruitment hospital [8] 25008 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [9] 25009 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [10] 25010 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [11] 25011 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [12] 25012 0
Concord Repatriation Hospital - Concord
Recruitment hospital [13] 25013 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [14] 25014 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [15] 25015 0
The Canberra Hospital - Garran
Recruitment hospital [16] 25016 0
Blacktown Hospital - Blacktown
Recruitment hospital [17] 25017 0
The Northern Hospital - Epping
Recruitment hospital [18] 25018 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [19] 25041 0
The Townsville Hospital - Douglas
Recruitment hospital [20] 25042 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [21] 25043 0
Gold Coast University Hospital - Southport
Recruitment hospital [22] 25044 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [23] 25045 0
North Shore Private Hospital - St Leonards
Recruitment hospital [24] 25066 0
Coastal Digestive Health - Maroochydore
Recruitment postcode(s) [1] 40660 0
4101 - South Brisbane
Recruitment postcode(s) [2] 40661 0
4029 - Herston
Recruitment postcode(s) [3] 40662 0
2170 - Liverpool
Recruitment postcode(s) [4] 40663 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 40664 0
3004 - Melbourne
Recruitment postcode(s) [6] 40665 0
3065 - Fitzroy
Recruitment postcode(s) [7] 40666 0
3128 - Box Hill
Recruitment postcode(s) [8] 40667 0
3084 - Heidelberg
Recruitment postcode(s) [9] 40668 0
5000 - Adelaide
Recruitment postcode(s) [10] 40669 0
6008 - Subiaco
Recruitment postcode(s) [11] 40670 0
4575 - Birtinya
Recruitment postcode(s) [12] 40671 0
2139 - Concord
Recruitment postcode(s) [13] 40672 0
3050 - Parkville
Recruitment postcode(s) [14] 40673 0
6150 - Murdoch
Recruitment postcode(s) [15] 40674 0
2605 - Garran
Recruitment postcode(s) [16] 40675 0
2148 - Blacktown
Recruitment postcode(s) [17] 40676 0
3076 - Epping
Recruitment postcode(s) [18] 40677 0
5011 - Woodville
Recruitment postcode(s) [19] 40702 0
4814 - Douglas
Recruitment postcode(s) [20] 40703 0
5042 - Bedford Park
Recruitment postcode(s) [21] 40704 0
4215 - Southport
Recruitment postcode(s) [22] 40705 0
3168 - Clayton
Recruitment postcode(s) [23] 40706 0
2065 - St Leonards
Recruitment postcode(s) [24] 40729 0
4558 - Maroochydore

Funding & Sponsors
Funding source category [1] 314192 0
Commercial sector/Industry
Name [1] 314192 0
Janssen-Cilag Pty Ltd
Country [1] 314192 0
Australia
Primary sponsor type
Other
Name
Mater Research Institute
Address
Level 3, Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 316113 0
University
Name [1] 316113 0
The University of Queensland
Address [1] 316113 0
St Lucia QLD 4072
Country [1] 316113 0
Australia
Other collaborator category [1] 282726 0
Other Collaborative groups
Name [1] 282726 0
Australia New Zealand Inflammatory Bowel Disease Consortium
Address [1] 282726 0
Level 2, Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Country [1] 282726 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313319 0
Royal Brisbane & Women's Hospital Human Research Ethics Committee (RBWH HREC)
Ethics committee address [1] 313319 0
Ethics committee country [1] 313319 0
Australia
Date submitted for ethics approval [1] 313319 0
16/02/2019
Approval date [1] 313319 0
18/03/2019
Ethics approval number [1] 313319 0
HREC/2019/QRBW/49250
Ethics committee name [2] 313321 0
Mater Misericordiae Ltd Human Research Ethics Committee
Ethics committee address [2] 313321 0
Ethics committee country [2] 313321 0
Australia
Date submitted for ethics approval [2] 313321 0
02/08/2019
Approval date [2] 313321 0
31/10/2019
Ethics approval number [2] 313321 0
HREC/MML/56171

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

Contacts
Principal investigator
Name 127722 0
A/Prof Jakob Begun
Address 127722 0
Mater IBD Research Group
Level 2, Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Country 127722 0
Australia
Phone 127722 0
+61 730105788
Fax 127722 0
Email 127722 0
[email protected]
Contact person for public queries
Name 127723 0
Jakob Begun
Address 127723 0
Mater IBD Research Group
Level 2, Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Country 127723 0
Australia
Phone 127723 0
+61 730105788
Fax 127723 0
Email 127723 0
[email protected]
Contact person for scientific queries
Name 127724 0
Jakob Begun
Address 127724 0
Mater IBD Research Group
Level 2, Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Country 127724 0
Australia
Phone 127724 0
+61 730105788
Fax 127724 0
Email 127724 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


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.