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Trial registered on ANZCTR


Registration number
ACTRN12618000076279
Ethics application status
Approved
Date submitted
8/01/2018
Date registered
18/01/2018
Date last updated
5/02/2019
Date data sharing statement initially provided
19/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Trial of Amnion Cell Therapy for Ischaemic Stroke (I-ACT)
Scientific title
I-ACT: Phase I trial of Amnion Cell Therapy for Ischaemic Stroke to establish the maximum tolerable dose
Secondary ID [1] 293728 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Amnion Cell Therapy for Ischaemic Stroke (I-ACT)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischaemic Stroke 306092 0
Condition category
Condition code
Stroke 305218 305218 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
dose escalation of amnion stem cell. the dose is given once intravenously in the hospital after acute ischaemic stroke. The design is similar to 3+3 dose escalation. The first group of 3 patients receives 2 million cells/kg. the next group receives 4 million cells/kg. the next group receives 8 million cells/kg, then 16 million cells/kg and the final group receives 32 million cells/kg
Intervention code [1] 299979 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 304374 0
the maximal tolerable dose (MTD) is estimated using the BOIN package (R statistical foundation)
Timepoint [1] 304374 0
90 days post stroke onset
Primary outcome [2] 304446 0
We define a treatment-emergent adverse effect/AE (TEAE) as any event not present before the initiation of treatment or any event already present that worsened in either intensity or frequency after exposure to the study treatment. We classify TEAEs as mild, moderate, severe or life-threatening according to standard procedures. Dose-limiting toxicity (DLT) is defined here to be equivalent to SAE and includes any untoward effect such as death, life threatening, requires hospitalisation (for outpatient), prolonged hospitalisation (for inpatients) or requires intervention to prevent permanent damage.
Timepoint [2] 304446 0
90 days
Secondary outcome [1] 341759 0
National Institute of Health Stroke Scale (NIHSS)
Timepoint [1] 341759 0
90 days post stroke onset
Secondary outcome [2] 341760 0
volume of vasogenic oedema on MRI
Timepoint [2] 341760 0
5-7 days post stroke onset
Secondary outcome [3] 341761 0

Infarct expansion ratio on MRI (between initial MR scan and at 1 week)
Timepoint [3] 341761 0
5-7 days post stroke onset

Eligibility
Key inclusion criteria
Patients are eligible if:
1)-they have ischaemic stroke in the territory of the large main artery (middle cerebral artery); 2)- present within 24 hours of stroke onset and are not eligible for TPA or clot retrieval;
3)-age is between 18-85 years old;
4)-have National Institute of Health Stroke Scale/NIHSS (tool used in clinical trials for measuring stroke severity) between 6-15.
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients are excluded if there is evidence of:
1)-autoimmune disease, organ transplant, malignancy, splenectomised individuals, or have infection at the time of stroke;
2)-neurodegenerative disease such as dementia or Parkinson’s disease;
3)-pregnancy;
4)-have contra-indications for MR imaging [patients with initial infarct (on DWI) volume <5 ml will also be excluded. This is a common strategy used in many studies to exclude infarcts with very small volume and likely good outcome;
5) eligible for TPA and/or ECR;
6)-patients with mild stroke (NIHSS <6) or very severe stroke (NIHSS >15).

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
dose escalation 3+3
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Descriptive statistics will be used to describe patient demographics, safety and SAE of hAEC.

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)
VIC
Recruitment hospital [1] 9694 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 18463 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 298343 0
Government body
Name [1] 298343 0
NHMRC
Address [1] 298343 0
Physical address

16 Marcus Clarke St
Canberra ACT 2601
Postal address
National Health and Medical Research Council (NHMRC)
GPO Box 1421
Canberra ACT 2601
Country [1] 298343 0
Australia
Primary sponsor type
Individual
Name
Prof Thanh Phan
Address
Monash Medical Centre, Monash Health
246 Clayton Rd Clayton
VIC Australia 3168
Country
Australia
Secondary sponsor category [1] 297462 0
Hospital
Name [1] 297462 0
Monash Health
Address [1] 297462 0
246 Clayton Rd Clayton VIC Australia 3168
Country [1] 297462 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299336 0
The Monash Health Human Research Ethics Committee (HREC)
Ethics committee address [1] 299336 0
246 Clayton Rd Clayton VIC 3168
Ethics committee country [1] 299336 0
Australia
Date submitted for ethics approval [1] 299336 0
09/02/2018
Approval date [1] 299336 0
20/08/2018
Ethics approval number [1] 299336 0
RES-18-0000179A

Summary
Brief summary
This trial is a dose escalation study to determine the maximal tolerable dose of human amnion stem cell for the treatment of acute ischaemic stroke (focal brain ischaemia from blood clot obstructing the vessel lumen).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80098 0
Prof Thanh Phan
Address 80098 0
Monash Medical Centre, 246 Clayton Rd Clayton VIC 3168
Country 80098 0
Australia
Phone 80098 0
613-85722612
Fax 80098 0
613-95946241
Email 80098 0
thanh.phan@monash.edu
Contact person for public queries
Name 80099 0
Prof Thanh Phan
Address 80099 0
Monash Medical Centre, 246 Clayton Rd Clayton VIC 3168
Country 80099 0
Australia
Phone 80099 0
613-85722612
Fax 80099 0
613-95946241
Email 80099 0
thanh.phan@monash.edu
Contact person for scientific queries
Name 80100 0
Prof Thanh Phan
Address 80100 0
Monash Medical Centre, 246 Clayton Rd Clayton, VIC 3168
Country 80100 0
Australia
Phone 80100 0
613-85722612
Fax 80100 0
613-95946241
Email 80100 0
thanh.phan@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
de-identified data will be provided and analysed as a group
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Attachments/websites
Type [1] 845 0
Statistical analysis plan
URL/details/comments [1] 845 0
https://www.frontiersin.org/articles/10.3389/fneur.2018.00198/full
Attachment [1] 845 0
Summary results
Not applicable