PNEUMOSTEM for the Prevention and Treatment of Severe BPD in Premature Infants

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in which premature infants and it results in significant morbidity and mortality. PNEUMOSTEM is intended to prevent and treat BPD by modulating inflammation and repairing damaged lung tissue in premature infants through paracrine effects.

• PNEUMOSTEM (Biological): human umbilical cord blood-derived mesenchymal stem cells
• Placebo (Other): normal saline

Primary outcomes

• Percentage of subjects who have severe BPD or are dead [36 weeks postmenstrual age (PMA)]: Percentage of subjects who have severe BPD or are dead

Secondary outcomes

• Percentage of subjects who have moderate/severe BPD or are dead [36 weeks PMA]: Percentage of subjects who have moderate/severe BPD or are dead
• Percentage of subjects by severity of BPD [prenatal 28 days/36 weeks PMA]: Percentage of subjects by severity of BPD
• Percentage of subjects in death due to lung disease [prenatal 28 days/36 weeks PMA and study end timepoint]: Percentage of subjects in death due to lung disease
• intubation duration [up to 24 weeks]: intubation duration
• ventilation duration [up to 24 weeks]: ventilation duration
• continuous positive airway pressure (CPAP) treatment duration [up to 24 weeks]: continuous positive airway pressure (CPAP) treatment duration
• treatment duration with supplemental oxygen [up to 24 weeks]: treatment duration with supplemental oxygen
• % of subjects treated with steroid for weaning ventilator [up to 24 weeks]: % of subjects treated with steroid for weaning ventilator
• Retinopathy of prematurity (ROP) with stage III or higher [up to 24 weeks]: number of subjects with ROP with stage III or higher
• number of subjects with retinopathy of prematurity that needs bevacizumab or laser therapy [up to 24 weeks]: number of subjects with retinopathy of prematurity that needs bevacizumab or laser therapy
• z-score [up to 24 weeks (visit 10)]: percentile for body weight, height, and head circumference
• days in hospitalization [up to 24 weeks]: days in hospitalization
• changes in tracheal suction fluid examination [from screening to 7 days after IP administration (visit 5)]: changes in tracheal suction fluid examination

Sex: All, ages: any to 13 Days

Inclusion Criteria:

at screening and randomization

1. 23 weeks to < 25 weeks of gestational age
2. 500g to 1,250g body weight at birth
3. premature infant within postnatal 13 days of age
4. use ventilator with ventilation rate >12 breaths/min or oxygen supply > 25%, or use high frequency ventilator (HFV)

at IP administration

1. premature infant within postnatal 5 to 14 days of age
2. No improvement in ventilator setting 24 hours prior to administration of IP

Exclusion Criteria:

1. subject with cyanotic congenital heart disease or non-cyanotic congenital heart disease that can cause heart failure
2. subject with pulmonary hypoplasia, congenital diaphragmatic hernia, or serious lung malformation such as congenital cystic lung disease
3. subject with chromosome disorder with serious malformation (i.e. Edward syndrome, patau syndrome, Down syndrome, etc.), severe congenital malformation (i.e. hydrocephalus, encephalocele, etc.), or severe congenital infection (i.e., herpes, toxoplasmosis, rubella, syphilis, AIDS, etc.)
4. subject with serious sepsis as active infection or shock due to sepsis
5. subject with grade 3 or 4 of bilateral intraventricular hemorrhage
6. at screening, subject with active pulmonary hemorrhage or active air leak syndrome
7. subject who underwent/will undergo surgery within 72 hours before/after investigational product (IP) administration
8. subject who is expected to be treated with surfactant within 24 hours prior to IP administration
9. subject who is expected to be allergic to gentamicin (Birth mother's allergy for gentamicin will be confirmed).
10. subject who have previously participated in other clinical trials
11. subject who is considered ineligible by investigator due to other medical reasons

• Results publication: Ahn SY, Chang YS, Lee MH, Sung SI, Lee BS, Kim KS, Kim AR, Park WS. Stem cells for bronchopulmonary dysplasia in preterm infants: A randomized controlled phase II trial. Stem Cells Transl Med. 2021 Aug;10(8):1129-1137. doi: 10.1002/sctm.20-0330. Epub 2021 Apr 20. PMID 33876883

• Wonsoon Park, Principal investigator, Samsung Medical Center
• Airhan Kim, Principal investigator, Asan Medical Center