PNEUMOSTEM® for Improving Respiratory Outcomes in Very Premature Infants Diagnosed With Early Pulmonary Arterial Hypertension

Official title

A Clinical Study of Advanced Regenerative Medicine to Evaluate the Safety and Potential Efficacy of PNEUMOSTEM® for Improving Respiratory Outcomes in Very Premature Infants Diagnosed With Early Pulmonary Arterial Hypertension

Overview

The goal of this clinical trial is to evaluate the safety and potential efficacy of PNEUMOSTEM® for improving respiratory outcomes in very premature infants diagnosed with Early Pulmonary Arterial Hypertension. The main questions it aims to answer are: * In very premature infants diagnosed with early pulmonary arterial hypertension, will a single intratracheal administration of PNEUMOSTEM®(Allogeneic umbilical cord blood-derived mesenchymal stem cells) result in improvement of pulmonary arterial hypertension based on echocardiographic assessment? * In very premature infants diagnosed with early pulmonary arterial hypertension who show improvement of pulmonary arterial hypertension based on echocardiographic assessment following a single intratracheal administration of PNEUMOSTEM®(Allogeneic umbilical cord blood-derived mesenchymal stem cells), at what time point does this improvement occur? Participants will: * Single intratracheal dose of PNEUMOSTEM® at 2.0 x 10,000,000 cells/kg * Acute adverse event monitoring: 24 hours post-administration for safety assessment * Follow- up time points: Day 1(Baseline, PNEUMOSTEM® administration), Day 2, Week 1, Week 2, Postnatal Day 28, PMA 36\~40 weeks

Interventions

• Biological PNEUMOSTEM®
  PNEUMOSTEM® will be administered intratracheally as a single dose of 2.0x10000000 cells/kg on Day 1.

Primary outcome measures

• Time point(week) of complete reversal of cardiac shunt direction [Time frame: Biweekly from day after PNEUMOSTEM administration until postnatal day 28]
• Time to normalization of ventricular septal configuration [Time frame: Once between postnatal day 28 and PMA 36~40 weeks]
• Change in duration of pulmonary hypertension medication use [Time frame: Daily on PNEUMOSTEM administration day and the next day]
• Change in duration of mechanical ventilation [Time frame: Weekly at week 1 and week 2 after PNEUMOSTEM administration]
• Change in duration of supplemental oxygen therapy. [Time frame: Weekly at week 1 and week 2 after PNEUMOSTEM administration]
• Incidence of Bronchopulmonary Dysplasia(BPD) [Time frame: At postnatal day 28 and at between PMA 36~40 weeks]
• Severity of Bronchopulmonary Dysplasia(BPD) [Time frame: At postnatal day 28 and at between PMA 36~40 weeks]
• Incidence of Retinopathy of Prematurity(ROP) [Time frame: Once at between PMA 36~40 weeks]
• Severity of Retinopathy of Prematurity(ROP) [Time frame: Once at between PMA 36~40 weeks]
• Time point of brain injury ditection on Brain MRI [Time frame: Once at between PMA 36~40 weeks]

Secondary outcome measures (12)

• Incidence of Adverse Events Assessed by latest version of CTCAE [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]
• Change in anthropometric measurements - Weight [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]
• Change in anthropometric measurements - Head Circumference [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]
• Abnormal findings on physical examination - Skin and Head/Neck [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]
• Abnormal findings on physical examination - Cardiovascular and Respiratory systems [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]
• Abnormal findings on physical examination - Abdomen and Genitalia [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]
• Abnormal findings on physical examination - Nervous and Musculoskeletal systems [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]
• Change in vital signs - Blood pressure [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]
• Change in vital signs - Body temperature [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]
• Change in vital signs - Heart rate [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]
• Change in vital signs - Respiratory rate [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]
• Change in vital signs - Oxygen saturation [Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks]

Eligibility criteria

Inclusion criteria

• Premature infants within 2 weeks of birth with a gestational age of 28 weeks or less or birth weight of less than 1,250g who require continuous invasive mechanical ventilation
• When diagnosed with early pulmonary arterial hypertension satisfying condition ① or ② up to 14 days after birth:

• When on or more of the following abnormal findings are present on echocardiography performed between 4 and 14 days after birth (findings at 1-3 days after birth correspond to early neonatal transition):

• Sytemic or suprasystemic pulmonary artery pressure >40mmHg(based on peak Doppler velocity of tricuspid regurgitation)
• Right-to-left or bidirectional shunt through patent ductus arteriosus, foramen ovale, or atrial septal defect
• Flattened interventricular septum or D-shaped left ventricle at end systole ② When receiving nitric oxide(NO) inhalation therapy for persistent pulmonary hypertension of the newborn(PPHN) within 3 days after birth

Exclusion criteria

• Those witth cyanotic congenital heart defects or acyanotic congenital heart defects causing heart failure, excluding patent ductus arteriosus in premature infatns
• Those with severe pulmonary malformations such as congenital diaphragmatic hernia or congenital cystic lung disease
• Those who underwent surgery within 72 hours before or after administration of the investigational cell product, or those for whom surgery is anticipated
• Those who received surfactant within 24 hours prior to administration of the investigattional cell product
• Those with chromosomal abnormalities accompanied by severe malformations(such as Edwards syndrome, Patau syndrome, Down syndrome, etc.) and severe congenital malformations(such as hydrocephalus, encephalocele, etc.)
• Those with severe congenital infectious diseases(such as herpes, toxoplasmosis, rubella, syphilis, AIDS, etc.)
• Those with severe sepsis or shock due to active infection not adequately treated with antibiotics
• Those who have a history of participation in other advanced regenerative medicine clinical studies or clinical trials
• Others deemed inappropriate by tthe investigator to participate in this advanced regenerative medicine clinical study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Samsung Medical Center, 81, Irwon-ro, Gangnam-gu, Seoul, Republic of Korea — Seoul

Identifiers

NCT: NCT07368088 · 2025-10-080

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗