Trial registered on ANZCTR


Trial ID
ACTRN12616001385437
Ethics application status
Approved
Date submitted
23/09/2016
Date registered
6/10/2016
Date last updated
7/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Intravenous Immunoglobulin (IVIg) in Spinal Cord Injury
Scientific title
Assessing feasibility, safety and efficacy of IVIg therapy in patients with acute traumatic spinal cord injury
Secondary ID [1] 290209 0
Nil known
Universal Trial Number (UTN)
U1111-1187-9726
Trial acronym
INFUSE Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal Cord Injury 300376 0
Condition category
Condition code
Injuries and Accidents 300239 300239 0 0
Other injuries and accidents
Neurological 300297 300297 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Privigen, i.e. liquid human Immunoglobulin preparation (10% w/v), will be administered intravenously in two doses. The first dose will be given within 12 hours of acute traumatic cervical or thoracic spinal cord injury. The second dose will be administered the following day. Each dose will be calculated to 1g/kg of the patient's body weight.
Intervention code [1] 295972 0
Treatment: Drugs
Comparator / control treatment
A control group will be assembled from de-identified patient records for baseline data, which will be extracted from existing databases at the Princess Alexandra Hospital. Control patients would have been admitted to and received their care from the Princess Alexandra Hospital between January 2012 and July 2019. Control subjects will have received standard clinical care without IVIg treatment, and they will be matched as closely as possible to participants in the treatment arm in terms of age, sex, mode and type of spinal cord injury at the outset.
Control group
Historical

Outcomes
Primary outcome [1] 299716 0
To obtain exploratory data on the efficacy of IVIg infusion in patients with acute traumatic spinal cord injury. The functional outcome will be assessed via:

a) ASIA examinations (standard neurological assessment tool) to assess neurological (sensory and motor) impairment at set intervals post-accident
b) SCIM (Spinal Cord Independence Measure) questionnaires, which assess both function and independence.
Timepoint [1] 299716 0
The severity and level of neurological impairment for each study participant will be assessed upon admission, and then again at day 1, 3, 7, 21, 42 post-injury and at patient discharge (~12 months post-injury) from the Princess Alexandra Hospital, Brisbane.
Secondary outcome [1] 327936 0
To monitor patient safety during and following IVIg infusion in individuals with acute traumatic spinal cord injury. Complications will be reviewed, assessed and managed as clinically indicated. The research team will record adverse events (complications) and report any Serious Adverse Events to the Metro South HREC and other authorised parties as stipulated in the Clinical Trial Agreement.
Timepoint [1] 327936 0
Complications will be monitored, recorded and reported on in a contemporaneous method throughout the participants inpatient stay at Princess Alexandra Hospital, Brisbane.
Secondary outcome [2] 328179 0
To explore the feasibility of initiating IVIg treatment in SCI patients within 12 hours of their accident.
Timepoint [2] 328179 0
Potential barriers to initiating IVIg treatment within 12 hours of injury / upon admission to the Princess Alexandra Hospital, e.g. due to complications, hospital delays, etc. that could see a patient missing out on acceptance into the study and/or treatment being terminated will be documented and reported upon.
Secondary outcome [3] 328180 0
To explore the pharmacokinetics of IVIg in SCI patients
Timepoint [3] 328180 0
We will measure immunoglobulin levels and other biomarkers of injury / inflammation in the blood of study participants via serum assay upon admission, and then again at 1, 3, 7, 21, 42 days post-injury plus on patient discharge.

Eligibility
Key inclusion criteria
Acute traumatic cervical or thoracic spinal cord injury (up to T9).
Initiation of IVIg treatment must be within 12 hours of injury.
Minimum age
16 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known hypersensitivity to Privigen
2. History of significant cardiovascular, liver or kidney disease
3. Unconscious
4. Penetrating spinal cord injury
5. Involvement in another SCI research project
6. Presence of a mental disorder or other illness, which, in the view of the Principle Investigator (or their delegate) precludes informed consent and/or accurate medical evaluation.
7. Patients with history of regular substance abuse
8. Inability to commit or be available for follow-ups.

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 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Exploratory analysis of study outcomes will involve Student’s t-test and multivariate analysis (e.g. one- or two-way ANOVA with post-hoc) as appropriate. Comparisons will be made against baseline data on expected outcomes based on historical data from patients that were closely matched for key parameters, incl. age, sex, cause and severity of injury, etc.

Recruitment
Recruitment status
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)
QLD
Recruitment hospital [1] 6714 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 14358 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 294572 0
Commercial sector/Industry
Name [1] 294572 0
CSL Behring AG
Address [1] 294572 0
Wankdorf Strasse 10, Bern 3014
Country [1] 294572 0
Switzerland
Primary sponsor type
University
Name
University of Queensland
Address
Brisbane, QLD 4072
Country
Australia
Secondary sponsor category [1] 293440 0
Commercial sector/Industry
Name [1] 293440 0
CSL Behring AG
Address [1] 293440 0
Wankdorf Strasse 10, 3014 Bern, Switzerland
Country [1] 293440 0
Switzerland

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296005 0
Metro South HREC
Ethics committee address [1] 296005 0
PAH Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 296005 0
Australia
Date submitted for ethics approval [1] 296005 0
14/03/2016
Approval date [1] 296005 0
19/04/2016
Ethics approval number [1] 296005 0
HREC/16/QPAH/196
Ethics committee name [2] 296070 0
UQ Medical Research Ehics Committee
Ethics committee address [2] 296070 0
Human Ethics, Research Management Office,
UQ Research and Innovation
The University of Queensland
Cumbrae-Stewart Building #72
Brisbane, QLD 4072
Ethics committee country [2] 296070 0
Australia
Date submitted for ethics approval [2] 296070 0
19/04/2016
Approval date [2] 296070 0
28/07/2016
Ethics approval number [2] 296070 0
2016001156

Summary
Brief summary
Our extensive pre-clinical studies have indicated that intravenous immunoglobulin (IVIg) therapy is highly beneficial and significantly improves the neurological recovery if administered during the acute phase of SCI. As IVIg is already in clinical use as an immunomodulatory treatment for a variety of other disorders (incl. neurological conditions) and has a good safety profile, we now wish to explore the feasibility of treating human patients that have suffered either a cervical or thoracic spinal cord injury with IVIg.

The specific aims of our Phase 1 study are as follows:
1) To test the feasibility of delivering IVIg within 12 hours of acute traumatic SCI.
2) To obtain data on the safety of IVIg in SCI using registry data for comparison.
3) To study the pharmacokinetics of IVIg in SCI
4) To relate the pharmacology of IVIg in SCI to safety and outcome measures
5) To obtain exploratory pilot data on the effect of IVIg treatment on the neurological outcome.

Blood samples will be used for assessment of biomarkers of injury (e.g. cytokines) and studies on the pharmacological properties (e.g. half-life) of IVIg in the context of SCI. Serious adverse events will be recorded and compared to registry data / untreated patients to explore a possible (though unexpected) relationship with IVIg treatment. Suitable controls will be identified based on age, gender, nature and level of injury. De-identified data on the functional outcome of these individuals will also be used to obtain exploratory pilot data on therapeutic efficacy of IVIg.

All participants will be followed for up to a year after their injury at set intervals, using physical examination to accurately determine motor and sensory recovery and questionnaires which would indicate functionality and social and emotional states.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1129 1129 0 0
http://www.anzctr.org.au/AnzctrAttachments/371550-ACN3-3-495.pdf (Publication)

Contacts
Principal investigator
Name 69258 0
Dr Marc Ruitenberg
Address 69258 0
School of Biomedical sciences, Faculty of Medicine, The University of Queensland 4072, Brisbane, Australia
Country 69258 0
Australia
Phone 69258 0
+617 3346 7602
Fax 69258 0
+61 7 3365 1766
Email 69258 0
m.ruitenberg@uq.edu.au
Contact person for public queries
Name 69259 0
Mrs Esther Jacobson
Address 69259 0
University of Queensland, Level 7, Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102
Country 69259 0
Australia
Phone 69259 0
+61 7 3443 7290
Fax 69259 0
Email 69259 0
e.jacobson@uq.edu.au
Contact person for scientific queries
Name 69260 0
Dr Marc Ruitenberg
Address 69260 0
School of Biomedical sciences, Faculty of Medicine, The University of Queensland 4072, Brisbane, Australia
Country 69260 0
Australia
Phone 69260 0
+617 3346 7602
Fax 69260 0
+61 7 3365 1766
Email 69260 0
m.ruitenberg@uq.edu.au