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Trial registered on ANZCTR


Registration number
ACTRN12622000588796p
Ethics application status
Not yet submitted
Date submitted
15/12/2021
Date registered
20/04/2022
Date last updated
20/04/2022
Date data sharing statement initially provided
20/04/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
ACT2: Phase 2 trial of Amnion Cell Therapy for Ischaemic Stroke
Scientific title
ACT2: Phase 2 trial of Amnion Cell Therapy for Ischaemic Stroke on Disability After Ischaemic Stroke
Secondary ID [1] 306275 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
ACT2
Linked study record
This study is linked the ACT-I Phase I trial (ACTRN12618000076279) . The previous study was a dose escalation study.

Health condition
Health condition(s) or problem(s) studied:
Stroke 323316 0
Ischaemic stroke 323317 0
Condition category
Condition code
Stroke 320880 320880 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
amnion stem cell will be given by hospital nurse as set dose of 230 million cells or 460 million cells or placebo in the hospital. Patients will be given 230 millions human amnion epithelial cells (hAECs) by intravenous infusion over 2 hours, previously shown to be safe in preterm babies and acute stroke patients. For patients receiving 460 millions hAECs, the treatment will be given over 2 days. This will be done using a standard infusion pump with an agitator to prevent clumping of cells. Each bag has a volume of 200-250 ml. Prior to infusion, the line is primed with cells so that there is no wastage. The bag is disconnected and the intravenous bung (stopper) is flushed with 10 ml of saline at the end of infusion. Adherence to therapy will be determined by assessing the remnant of the hAEC infusion bag at the end of each treatment
Intervention code [1] 321488 0
Treatment: Other
Comparator / control treatment
best medical therapy versus amnion stem cell therapy. Best medical therapy is defined as stroke unit care.
Control group
Active

Outcomes
Primary outcome [1] 328674 0
degree of disability after stroke as assessed by modified Rankin score, Modified Rankin score 0-2 equates to no disability and 3-6 to disability.
Timepoint [1] 328674 0
90 days after stroke onset.
Secondary outcome [1] 399920 0
The secondary outcome is change in stroke severity as assessed by National Institute of Health Stroke Scale (NIHSS). Clinical improvement is defined as decrement in NIHSS greater or equal to 4 points.
Timepoint [1] 399920 0
Change in NIHSS is performed at 1 week post stroke.
Secondary outcome [2] 407417 0
The modified Rankin Scale (mRS) will be performed at 12 months and will be used to evaluate safety of human amnion epithelial cells (hAECs).
Timepoint [2] 407417 0
12 months post infusion
Secondary outcome [3] 407418 0
The proportion of patients with change in infarct expansion ratio (IER) between the outcome post-treatment (T2 FLAIR) infarct volume and the initial DWI infarct volume.
Timepoint [3] 407418 0
1 week post infusion
Secondary outcome [4] 407419 0
proportion of patients with symptomatic intracerebral haemorrhage on CT or MRI scans.
Timepoint [4] 407419 0
1 week post infusion

Eligibility
Key inclusion criteria
Patients are eligible if 1) age is between 18-85 years old; 2) they present within 24 hours of stroke onset; 3) have National Institute of Health Stroke Scale/NIHSS (tool used in clinical trials for measuring stroke severity) between 6-20; 4) have ischaemic stroke in the territory of the large vessel 26; 5) have less than a 4 point change in NIHSS after receiving Alteplase or Tenecteplase; 6) have less than an 8 point change in NIHSS after receiving clot retrieval; 7) the patient or person responsible (on behalf of participant) signs a consent form after explanation of the trial.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients are excluded if 1) there is evidence of improvement after thrombolysis or thrombectomy; 2) they have autoimmune disease, organ transplant, malignancy, are splenectomised, or have infection at the time of stroke 3) they have neurodegenerative disease such as dementia or Parkinson’s disease; 4) are pregnant; 5) have contra-indications for magnetic resonance (MR) imaging such as a pacemaker; 6) initial infarct (on DWI) volume is less or equal to 5 ml or greater than 100 ml 5, 27; 7) they have mild stroke (NIHSS <6) or very severe stroke (NIHSS >20). This is a common strategy used in many studies to exclude infarcts with very small volume and likely good spontaneous outcome; very large infarcts are excluded as these patients have high probability of developing malignant middle cerebral artery infarction and death. Further exclusion criteria are 8) blood sugar level less or equal to 3 mml/L or equal or greater than 20 mmol/L; 9) significant lung disease requiring oxygen; 10) severe renal impairment.

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)
Allocation concealment of intravenous infusion: The intravenous fluid (infusion) bags will be sent from the facility enclosed in opaque amber material such that the clinical team providing therapy will not be able to identify the type of fluid (cell suspension or placebo). A tube connecting the infusion bag to the intravenous bung will also be enclosed by amber opaque material
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A central block randomization with block size 3 will ensure sufficient balance between treatment groups throughout recruitment.
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
covariate adjusted logistic regression

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/09/2022
Actual
Date of last participant enrolment
Anticipated
3/09/2024
Actual
Date of last data collection
Anticipated
2/09/2025
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 21563 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 36475 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 309493 0
Government body
Name [1] 309493 0
NHMRC
Country [1] 309493 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
246 Clayton Rd Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 310465 0
None
Name [1] 310465 0
Address [1] 310465 0
Country [1] 310465 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 309278 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 309278 0
246 Clayton Rd Clayton 3168 VIC Australia
Ethics committee country [1] 309278 0
Australia
Date submitted for ethics approval [1] 309278 0
02/05/2022
Approval date [1] 309278 0
Ethics approval number [1] 309278 0

Summary
Brief summary
Human amnion epithelial cells (hAECs) therapy attenuated infarct growth even when administered 3 days after the onset of stroke. The mechanisms of action involved modulation of the immune response to minimise further injury in the peri-infarct region. Our recent Phase 1 trial has now shown that amniotic stem cells can be given safely at up to 8 million cells/kg i.v.. We thus now propose a Phase 2 dose escalation trial providing a platform for a Phase 3 trial at a later stage. The design is based on the 1:1:1 randomisation (placebo versus 230 million cells or 460 million cells). Based on our published experimental findings and Phase I dose-escalation human safety trial, we hypothesise that hAECs therapy will reduce stroke disability.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113602 0
Prof Thanh Phan
Address 113602 0
Monash Medical Centre, 246 Clayton Rd Clayton, VIC 3168 Australia
Country 113602 0
Australia
Phone 113602 0
+61385722612
Fax 113602 0
+61395946241
Email 113602 0
[email protected]
Contact person for public queries
Name 113603 0
Thanh Phan
Address 113603 0
Monash Medical Centre, 246 Clayton Rd Clayton, VIC 3168 Australia
Country 113603 0
Australia
Phone 113603 0
+61385722612
Fax 113603 0
+61395946241
Email 113603 0
[email protected]
Contact person for scientific queries
Name 113604 0
Thanh Phan
Address 113604 0
Monash Medical Centre, 246 Clayton Rd Clayton, VIC 3168 Australia
Country 113604 0
Australia
Phone 113604 0
+61385722612
Fax 113604 0
+61395946241
Email 113604 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Trial data including individual participant data
When will data be available (start and end dates)?
available for 5 years after publications
Available to whom?
researchers on request
Available for what types of analyses?
individual patient data meta-analyses
How or where can data be obtained?
contact principle investigator: [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12944Study protocol    Protocol paper is being written



Results publications and other study-related documents

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