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

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

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

Inclusion Criteria:

1. 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

2. 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):

     1. Sytemic or suprasystemic pulmonary artery pressure >40mmHg(based on peak Doppler velocity of tricuspid regurgitation)
     2. Right-to-left or bidirectional shunt through patent ductus arteriosus, foramen ovale, or atrial septal defect
     3. 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:

1. Those witth cyanotic congenital heart defects or acyanotic congenital heart defects causing heart failure, excluding patent ductus arteriosus in premature infatns
2. Those with severe pulmonary malformations such as congenital diaphragmatic hernia or congenital cystic lung disease
3. Those who underwent surgery within 72 hours before or after administration of the investigational cell product, or those for whom surgery is anticipated
4. Those who received surfactant within 24 hours prior to administration of the investigattional cell product
5. 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.)
6. Those with severe congenital infectious diseases(such as herpes, toxoplasmosis, rubella, syphilis, AIDS, etc.)
7. Those with severe sepsis or shock due to active infection not adequately treated with antibiotics
8. Those who have a history of participation in other advanced regenerative medicine clinical studies or clinical trials
9. Others deemed inappropriate by tthe investigator to participate in this advanced regenerative medicine clinical study