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Trial registered on ANZCTR


Registration number
ACTRN12624000145505
Ethics application status
Approved
Date submitted
14/12/2023
Date registered
15/02/2024
Date last updated
4/06/2024
Date data sharing statement initially provided
15/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
NEOSTeM (NEOnatal STroke Mesenchymal Stem Cell) Trial: Assessing the Safety of Mesenchymal Stem Cells for Babies with Stroke
Scientific title
A Phase I Dose Escalation Safety Trial of Repeated Mesenchymal Stem Cell Treatment for Neonatal Stroke
Secondary ID [1] 309105 0
None
Universal Trial Number (UTN)
Trial acronym
NEOSTeM Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Term/near term neonatal stroke 329186 0
Condition category
Condition code
Neurological 326151 326151 0 0
Other neurological disorders
Stroke 329219 329219 0 0
Ischaemic
Reproductive Health and Childbirth 329220 329220 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Allogenic mesenchymal stem/stromal cells (MSCs). Supplied and formulated in cryoprotectant medium. The product is cryopreserved in the vapour phase of liquid nitrogen (cells prepared/manufactured years in advance). Prior to intravenous administration, the product is rapid-thawed at the clinical site in a neonatal intensive care setting.

Participants are treated in this dose-escalations study at 2- (low dose) or 5-million (high dose) cells/kg body weight. Enrollment across the two groups occurs sequentially. Treatment is administered twice. The first dose will commence within 72 hours of stroke confirmation via MRI, with the second 48-72 hours later. Intervention administration, dosing and adherence are recorded in site logs.
Intervention code [1] 325551 0
Treatment: Other
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334023 0
To assess the immediate safety of MSCs for neonatal stroke assessed via the occurrence of AEs and SAEs. All safety events will be captured, with some prespecified and graded based on severity. These include infusion reactions, infection, local site reactions and changes to vital signs and respiratory support. Data are collected from medical records and continuous physiological monitoring within neonatal intensive care.
Timepoint [1] 334023 0
During each infusion and up to 48 hours after the last infusion. Formal reporting of vitals will be taken immediately prior to the infusion, every 5 minutes during the infusion, 15 minutes after the infusion and then every 4 hourly or as clinically indicated.
Secondary outcome [1] 419121 0
To assess the follow-up safety of MSCs for neonatal stroke via the occurrence of AEs and SAEs. All safety events will be captured, with some assessed against prespecified outcomes and graded based on severity. Follow up will occur either during hospital stay in-person, via Telehealth/phone call if discharged or via in-person follow-ups (in-home or clinic).
Timepoint [1] 419121 0
Follow-up assesment with parent reported safety, including later emerging treatment reactions, changes to medical care/rehospitalisation or concerns from medical specialists at 7 and 14 days after the final infusion and at both 12-14 and 16-18 weeks term corrected age.
Secondary outcome [2] 419122 0
To assess the follow-up safety of MSCs for neonatal stroke via clinical assessments. Clinical assessments include General Movements Assessment, Hammersmith Infant Neurological Examination and the Hand Assessment for Infants. Together, these assessments predict long-term disability. Follow up will occur via in-person follow-ups (in-home or clinic).
Timepoint [2] 419122 0
Clinical assessments are completed at both 12-14 and 16-18 weeks term corrected age.
Secondary outcome [3] 419123 0
To evaluate the feasibility of treating with MSCs in neonates with stroke. Measured via summarised data of consent rate, recruitment rate, mean time to treat with first and second infusion and rate of capture of follow up clinical assessments at 12-14 and 16-18 weeks. All outcomes are assessed from study-specific records, with rate of capture of follow up assessed via study specific- and medical records.
Timepoint [3] 419123 0
Feasibility of treatment will be captured at various times spanning recruitment to study completion.
Secondary outcome [4] 431265 0
To evaluate the acceptability of treating with MSCs in neonates with stroke via parent acceptability questionnaires. These questionnaires were designed specifically for this study and comprise short prompts and 5-point Likert-scale responses. Sekon’s Theoretical Framework of Acceptability was used to guide questionnaires development, and drafts were piloted on consumer representatives.
Timepoint [4] 431265 0
Within the first week following participant treatment.
Secondary outcome [5] 431681 0
To evaluate the acceptability of treating with MSCs in neonates with stroke via clinician acceptability questionnaires. These questionnaires were designed specifically for this study and comprise short prompts and 5-point Likert-scale responses. Sekon’s Theoretical Framework of Acceptability was used to guide questionnaires development, and drafts were piloted on clinician representatives.
Timepoint [5] 431681 0
Within the first week following participant treatment.

Eligibility
Key inclusion criteria
1. Term/near-term infant greater than or equal to 35 weeks’ gestation
2. Diagnosis of a stroke within the first 21 days of life, characterized by predominantly unilateral ischemic lesion within the territory of the middle cerebral artery, as confirmed by MRI
3. Infant available for treatment within 72 hours from stroke confirmation
4. Informed consent obtained from the parent
Minimum age
No limit
Maximum age
21 Days
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Born <35 weeks’ gestation;
2. Stroke diagnosis made after 21 days of life;
3. Any proven or suspected congenital anomaly; chromosomal disorder or metabolic disorder;
4. Presence of an infection of the central nervous system;
5. Requiring or likely to require Extracorporeal Membrane Oxygenation (ECMO; contraindicated for cell therapy) life support;
6. Know positive test for HIV 1, HIV 2, hepatitis B virus, hepatitis C virus, or any other infection which in the opinion of the Investigator is likely to impact on the ability of the patient to participate in the study;
7. Venous thromboembolism currently receiving/requiring anti-coagulation;
8. No realistic prospect of survival (e.g. severe brain injury), at the discretion of the attending physician.

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
Dose-escalation
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
A formal Statistical Analysis Plan will not be developed for this study as it is a Phase I trial, with primary reporting of the occurrence and rate of AEs.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Commercial partner has withdrawn support and trial no longer has access to Investigational Product.
Date of first participant enrolment
Anticipated
3/05/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24151 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 24157 0
Monash Children’s Hospital - Clayton
Recruitment postcode(s) [1] 39683 0
2145 - Westmead
Recruitment postcode(s) [2] 39688 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 313084 0
Charities/Societies/Foundations
Name [1] 313084 0
White Coats Foundation
Country [1] 313084 0
Australia
Funding source category [2] 313307 0
Charities/Societies/Foundations
Name [2] 313307 0
Brain Australia
Country [2] 313307 0
Australia
Funding source category [3] 313308 0
Charities/Societies/Foundations
Name [3] 313308 0
Cerebral Palsy Alliance
Country [3] 313308 0
Australia
Primary sponsor type
Hospital
Name
Sydney Children's Hospital Network
Address
Cnr Hainsworth St and Hawkesbury Rd, Westmead, NSW 2145
Country
Australia
Secondary sponsor category [1] 317511 0
None
Name [1] 317511 0
Address [1] 317511 0
Country [1] 317511 0
Other collaborator category [1] 282574 0
Charities/Societies/Foundations
Name [1] 282574 0
Cerebral Palsy Alliance Research Institute
Address [1] 282574 0
Brain and Mind Centre, L4 B M02C, 88 Mallett Street, NSW
Country [1] 282574 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312329 0
Sydney Children's Hospital Network Human Research Ethics Committee
Ethics committee address [1] 312329 0
Cnr Hawkesbury Road and Hainsworth Street, Westmead, NSW Australia
Ethics committee country [1] 312329 0
Australia
Date submitted for ethics approval [1] 312329 0
17/02/2023
Approval date [1] 312329 0
11/05/2023
Ethics approval number [1] 312329 0
2023/ETH00169

Summary
Brief summary
Neonatal stroke occurs in up to 1 in 2,500 live births and can be defined as disturbances in the blood supply to the brain and includes an acute ischemic event. Up to 60% of babies diagnosed with stroke will have atypical neurological development and brain injury, including epilepsy and cerebral palsy. Current standard of care focusses on diagnosis and prompt stabilisation of symptoms such as seizures. There are no specific interventions to protect the developing brain or prevent the progression of injury. However, stem cells, particularly mesenchymal stem cells (MSCs), are a potential treatment for neonatal stroke, where early therapy may minimise lifelong impairment.

This Phase I dose escalation trial assesses the safety of early and repeated systemic (intravenous) administration of MSCs for neonatal stroke at both 2- and 5-million cells/kg body weight.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124274 0
Dr Himanshu Popat
Address 124274 0
Grace Centre for Newborn Intensive Care at The Children's Hospital at Westmead. Corner Hawkesbury Road and, Hainsworth St, Westmead NSW 2145
Country 124274 0
Australia
Phone 124274 0
+61 2 98452714
Fax 124274 0
Email 124274 0
[email protected]
Contact person for public queries
Name 124275 0
Madison Paton
Address 124275 0
Cerebral Palsy Alliance Research Institute. Brain and Mind Centre Level 4 88 Mallett Street, Camperdown, NSW 2050; Melbourne Office, 15 William St, Melbourne.
Country 124275 0
Australia
Phone 124275 0
+61 2 8052 2058
Fax 124275 0
Email 124275 0
[email protected]
Contact person for scientific queries
Name 124276 0
Madison Paton
Address 124276 0
Cerebral Palsy Alliance Research Institute. Brain and Mind Centre Level 4 88 Mallett Street, Camperdown, NSW 2050; Melbourne Office, 15 William St, Melbourne.
Country 124276 0
Australia
Phone 124276 0
+61 2 8052 2058
Fax 124276 0
Email 124276 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
No IPD for this trial be available at this stage. Any reasonable request for de-identified data at study completion will be considered by the Investigator team and Sponsor.


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.