iSTOP-CP

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Utrecht

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Decision date (initial)

2026-07-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The main objective of this study is to determine whether intranasal stem cell therapy (IN-MSC) can effectively reduce brain damage and improve motor outcomes in newborns with hypoxic-ischemic brain injury (HIBI). By conducting a placebo-controlled phase II clinical trial in infants with MRI confirmed HIBI, this trial wants to see if the treatment is effective and safe with the goal to eventually incorporate the therapy in standard clinical care.

Secondary objectives 5

1. To assess the efficacy of IN-MSCs to reduce the adverse effects of HIBI on neurodevelopment at 24 months of age.
2. To investigate the safety of IN-MSCs in infants with HIBI
3. To determine the neuroregenerative effects of IN-MSCs as determined on cranial MRI at 52 weeks PMA
4. Assessing the impact of intranasal MSC com-pared to standard supportive care on quality of life
5. Assessing the economic impact, cost-effectiveness, of intranasal MSC compared to standard supportive care

Conditions and MedDRA coding

Hypoxic-ischemic brain injury (HIBI) because of Perinatal Asphyxia (PA) or Perinatal arterial ischemic stroke (PAIS)

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board

Plan to share IPD

Yes

IPD plan description

This is requested in the informed consent form. Data will be shared upon request in a pseudonymized manner, in accordance with applicable privacy and data protection regulations.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Neonate with a gestational age ≥35.0 weeks at birth
2. Either a PAIS (a neurologic condition characterized by focal cerebral ischemia and infarction following blockage of a brain artery with impairment of blood supply and oxy-genation of brain tissue, clinically characterized by seizures (clinical or subclini-cal), respiratory difficulties, or both) or PA (defined as at least one out of the following: 5-min Apgar score ≤ 5, Resuscitation, Mechanical ventilation following resuscitation ≥ 10 minutes after birth, pH <7.0, BE <-16 mmol/L, or lactate > 10.0 mmol/L in umbilical cord blood sample, or in arterial, venous or capillary blood gas sample obtained within 1 hour after birth) diagnosis
3. Showing signs of hypoxic-ischemic injury in the following predefined brain areas (indicated by DWI restriction and/or abnormal ADC values and/or 1H-MRS lactate/N-acetyl aspartate (NAA) and/or NAA/Choline ratio abnormalities): PLIC (posterior limb of the internal capsule), central gray matter (BGT: basal ganglia and/or thalami), rolandic cortex, cerebral peduncles, white matter involving CST (corticospinal tract)
4. Written informed consent from custodial parent(s)

Exclusion criteria 3

1. Suspicion of chromosomal anomaly, metabolic disorder, genetic syndrome, congenital central nervous system (CNS) malformation, congenital CNS infection and main injury intracranial haemorrhage
2. Once a clinical team decides on withdrawal of NICU care, the patient is not eligible for inclusion: infants with very severe brain injury on MRI and need for ventilation support (not breathing independently), who have a prognosis of severely multiple handicaps and/or no realistic prospect of survival at the discretion of the attending physician, will not be eligible to iSTOP-CP, to avoid unnecessary suffering and an unacceptable quality of life
3. Contraindications for intranasal administration of medication, including nasal obstruction (e.g. choanal atresia), nasal septal abnormalities, nasal trauma, epistaxis, excessive nasal mucus or blood, and intranasal damage

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Bayley-IV-NL motor score assessed at 24 months of age.

Secondary endpoints 7

1. Cognitive development at 2 years, assessed using the cognitive composite Score of the Bayley-IV-NL
2. At 2 years of age, sensorineural disability will be assessed based on the presence of at least one of the following: cerebral palsy (GMFCS ≥1), neuromotor delay (Bayley-IV-NL motor score < -1 SD), cognitive delay (Bayley-IV-NL cognitive score < -1 SD), epilepsy (per ILAE definition), or moderate to severe visual or hearing impairment due to PA or PAIS.
3. At 3–4 months of age, safety will be evaluated by tracking adverse events occurring between IN-MSC administration and 3 months, and by assessing potential effects on the brain, including tumor formation, through MRI at 52 weeks postmenstrual age.
4. Between 3 and 24 months of age, safety will be monitored by tracking serious adverse events (e.g., seizures, unplanned hospital visits), use of additional medications, and any unexpected deviations in neurological development based on earlier MRI findings, using standardized assessments (GMA with MOS-R and HINE)
5. For infants with HIBI due to PA, the effect of IN-MSCs on white matter integrity will be assessed at 52 weeks PMA using DTI-MRI and tract-based FA analysis. For infants with PAIS, changes in brain tissue volume between the early neonatal MRI (<8 days) and MRI at 52 weeks PMA will be evaluated.
6. Differences in health-related quality of life (HRQoL) for patients and families will be assessed at 3, 9–12, and 24 months using questionnaires: EQ-5D-5L, PCL-5, LTO, KLIK Pain, CIS-4, and WEMWBS for parents/caregivers, and EQ-TIPS and PedsQL-Infant for infants
7. The economic impact at 24 months will be evaluated through a Health Technology Assessment, including a cost of illness study, societal return on investment, cost-effectiveness analysis, and budget impact analysis.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Utrecht

Sponsor organisation

Universitair Medisch Centrum Utrecht

Address

Heidelberglaan 100

City

Utrecht

Postcode

3584 CX

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Clinical trial contact

Public contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Clinical trial contact

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications