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

Study Overview
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Brief Summary
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This study is to evaluate the efficacy and safety of PNEUMOSTEM® for the Prevention and Treatment of Severe Bronchopulmonary Dysplasia (Severe BPD) in Premature Infants. Half of subjects will receive PNEUMOSTEM, while the other half will receive a placebo.

Detailed Description
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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.

Official Title
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A Multi-center, Randomized, Double-blind, Parallel, Placebo-controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of PNEUMOSTEM for the Prevention and Treatment of Severe Bronchopulmonary Dysplasia in Premature Infants

Conditions
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Severe Bronchopulmonary Dysplasia

Intervention / Treatment
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* Biological: PNEUMOSTEM
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: at screening and randomization 23 weeks to < 25 weeks of gestational age 500g to 1,250g body weight at birth premature infant within postnatal 13 days of age use ventilator with ventilation rate >12 breaths/min or oxygen supply > 25%, or use high frequency ventilator (HFV) at IP administration premature infant within postnatal 5 to 14 days of age No improvement in ventilator setting 24 hours prior to administration of IP Exclusion Criteria: subject with cyanotic congenital heart disease or non-cyanotic congenital heart disease that can cause heart failure subject with pulmonary hypoplasia, congenital diaphragmatic hernia, or serious lung malformation such as congenital cystic lung disease 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.) subject with serious sepsis as active infection or shock due to sepsis subject with grade 3 or 4 of bilateral intraventricular hemorrhage at screening, subject with active pulmonary hemorrhage or active air leak syndrome subject who underwent/will undergo surgery within 72 hours before/after investigational product (IP) administration subject who is expected to be treated with surfactant within 24 hours prior to IP administration subject who is expected to be allergic to gentamicin (Birth mother's allergy for gentamicin will be confirmed). subject who have previously participated in other clinical trials subject who is considered ineligible by investigator due to other medical reasons

Ages Eligible for Study
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Maximum Age: 13 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PNEUMOSTEM<br>human umbilical cord blood derived mesenchymal stem cell (hUCB-MSC) | Biological: PNEUMOSTEM<br>* human umbilical cord blood-derived mesenchymal stem cells<br>|
| Placebo Comparator: Placebo<br>normal saline | Other: Placebo<br>* normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects who have severe BPD or are dead | Percentage of subjects who have severe BPD or are dead | 36 weeks postmenstrual age (PMA) | 

Secondary Outcome Measures

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