Trial Outcomes & Findings for Perinatal Arterial Stroke Treated With Stromal Cells Intranasally (NCT NCT03356821)

Results Overview

The primary objective is to determine if MSC treatment in neonates with PAIS is safe and tolerable in the acute setting. This will be measured by the number of Participants with treatment-related adverse events after MSC treatment.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

10 participants

Primary outcome timeframe

24 hours after treatment

Results posted on

2024-05-13

Participant Flow

Between Feb 11, 2020, and April 29, 2021,10 infants were included in the PASSIoN trial. Neonates were eligible for the study if they had been born at one of the ten neonatal intensive care units (NICU) in the Netherlands and had signs of suspected PAIS. All eligible patients were transferred to the NICU of the Wilhelmina Children's Hospital (part of the University Medical Center, Utrecht, Netherlands) for confirmation of PAIS by MRI, then MSC treatment, within 7 days after presentation.

Participant milestones

Participant milestones
Measure	Mesenchymal Stem Cells Ten (near-)term newborns ≥36 weeks of gestation with or without clinical symptoms of PAIS but with a magnetic resonance imaging (MRI) confirmed PAIS (in the Middle Cerebral Artery region), and written parental consent were included this study. Mesenchymal Stem Cells: One dose of 50x10\^6 bone marrow-derived allogeneic MSCs via the nasal route as soon as possible after confirmation of the stroke (in the middle cerebral artery), but within the first week of onset of presenting clinical symptoms. Within 30 minutes after cleaning the nose with saline, using standard procedures operative at the Neonatal Intensive Care Unit, the MSC will be delivered.
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mesenchymal Stem Cells n=10 Participants All (near-)term newborns ≥36 weeks of gestation with or without clinical symptoms of PAIS but with a magnetic resonance imaging (MRI) confirmed PAIS (in the Middle Cerebral Artery region) will be eligible for this study. Following written parental consent, 10 patients will be included in our study. Mesenchymal Stem Cells: One dose of 50x10\^6 bone marrow-derived allogeneic MSCs via the nasal route as soon as possible after confirmation of the stroke (in the middle cerebral artery), but within the first week of onset of presenting clinical symptoms. Within 30 minutes after cleaning the nose with saline, using standard procedures operative at the Neonatal Intensive Care Unit, the MSC will be delivered.
Age, Continuous	40.3 weeks of gestational age at birth n=10 Participants
Sex: Female, Male Female	6 Participants n=10 Participants
Sex: Female, Male Male	4 Participants n=10 Participants
Birthweight	3415 gram n=10 Participants

PRIMARY outcome

Timeframe: 24 hours after treatment

The primary objective is to determine if MSC treatment in neonates with PAIS is safe and tolerable in the acute setting. This will be measured by the number of Participants with treatment-related adverse events after MSC treatment.

Outcome measures

Outcome measures
Measure	Mesenchymal Stem Cells n=10 Participants Ten (near-)term newborns ≥36 weeks of gestation with or without clinical symptoms of PAIS but with a magnetic resonance imaging (MRI) confirmed PAIS (in the Middle Cerebral Artery region), and written parental consent were included this study. Mesenchymal Stem Cells: One dose of 50x10\^6 bone marrow-derived allogeneic MSCs via the nasal route as soon as possible after confirmation of the stroke (in the middle cerebral artery), but within the first week of onset of presenting clinical symptoms. Within 30 minutes after cleaning the nose with saline, using standard procedures operative at the Neonatal Intensive Care Unit, the MSC will be delivered.
Number of Participants With Adverse Events Related to Intranasal MSC Treatment (Safety and Tolerability) in the Acute Setting. Serious adverse event · No	10 Participants
Number of Participants With Adverse Events Related to Intranasal MSC Treatment (Safety and Tolerability) in the Acute Setting. Serious adverse event · Yes	0 Participants
Number of Participants With Adverse Events Related to Intranasal MSC Treatment (Safety and Tolerability) in the Acute Setting. Adverse event: fever · No	9 Participants
Number of Participants With Adverse Events Related to Intranasal MSC Treatment (Safety and Tolerability) in the Acute Setting. Adverse event: fever · Yes	1 Participants

SECONDARY outcome

Timeframe: 3 months postnatal age

The secondary objective is to determine subacute and long-term safety of MSC treatment at 3 months. This will be measured by the occurence of treatment-related adverse events after the initial hospital stay, such as infections or cerebral tumorigenicity on MRI. Follow-up assessment at 3 months is part of regular care for neonates with PAIS.

Outcome measures

Outcome measures
Measure	Mesenchymal Stem Cells n=10 Participants Ten (near-)term newborns ≥36 weeks of gestation with or without clinical symptoms of PAIS but with a magnetic resonance imaging (MRI) confirmed PAIS (in the Middle Cerebral Artery region), and written parental consent were included this study. Mesenchymal Stem Cells: One dose of 50x10\^6 bone marrow-derived allogeneic MSCs via the nasal route as soon as possible after confirmation of the stroke (in the middle cerebral artery), but within the first week of onset of presenting clinical symptoms. Within 30 minutes after cleaning the nose with saline, using standard procedures operative at the Neonatal Intensive Care Unit, the MSC will be delivered.
Number of Participants With Adverse Events Related to Intranasal MSC Treatment (Safety and Tolerability) in the Subacute/Long-term Setting no subacute adverse events until 3 months of age	10 Participants
Number of Participants With Adverse Events Related to Intranasal MSC Treatment (Safety and Tolerability) in the Subacute/Long-term Setting subacute adverse events until 3 months of age	0 Participants

Adverse Events

Mesenchymal Stem Cells

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Mesenchymal Stem Cells n=10 participants at risk Ten (near-)term newborns ≥36 weeks of gestation with or without clinical symptoms of PAIS but with a magnetic resonance imaging (MRI) confirmed PAIS (in the Middle Cerebral Artery region), and written parental consent were included this study. Mesenchymal Stem Cells: One dose of 50x10\^6 bone marrow-derived allogeneic MSCs via the nasal route as soon as possible after confirmation of the stroke (in the middle cerebral artery), but within the first week of onset of presenting clinical symptoms. Within 30 minutes after cleaning the nose with saline, using standard procedures operative at the Neonatal Intensive Care Unit, the MSC will be delivered.
General disorders Fever	10.0% 1/10 • Treatment-related adverse events were monitored for 4 days after MSC administration (hospital stay), and until the age of 3 months (parent report).

Additional Information

Prof. M.J.N.L. Benders, MD, PhD, neonatologist

UMC Utrecht, The Netherlands

Phone: +31 88 755 5555

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place