Safety and Efficacy Evaluation of PNEUMOSTEM® Treatment in Premature Infants With Bronchopulmonary Dysplasia

Study Overview
=================
Brief Summary
-----------------
PNEUMOSTEM® is human umbilical cord blood derived mesenchymal stem cells and it is intended to treat premature infants with bronchopulmonary dysplasia. This study is to assess the safety and the efficacy of this study drug.

Detailed Description
-----------------
Bronchopulmonary dysplasia (BPD) is most common cause of death of children who were born prematurely, with low birth weights. In addition, many children who were recovered from this disease are suffering from many side effects such as prolonged hospitalization, pulmonary hypertension, and failure to thrive. The purpose of BPD treatment is to make a baby be able to do spontaneous breathing and to spontaneous breathing a baby needs much energy and because of this a baby may have difficulty to feed. For this reason, medication with steroid, diuretic and respiratory drugs are currently used. However, there is no effective cure so far. It has been reported that bone marrow derived mesenchymal stem cells (BM-MSC) can differentiate to pulmonary epithelial and pulmonary endothelial cells. Some animal studies showed that BM-MSC differentiated to bronchial cells and type 2 pneumocytes in rats with pneumonia and improve the fibrosis that occur after administration of bleomycin. Based on the findings, it is considered that mesenchymal stem cell therapy can help regenerate the damaged lung as well as BPD that cause lung inflammation, fibrosis, deficiency of type 2 pneumocytes, and so on. PNEUMOSTEM® is human umbilical cord blood derived mesenchymal stem cells and it is intended to treat premature infants with BPD. The main purpose of this study is to evaluate the safety and the tolerability of this study drug and to establish the maximum toxicity dose. The latent efficacy will also be assessed.

Official Title
-----------------
Open Label, Single-Center, Phase 1 Clinical Study to Evaluate the Safety and the Efficacy of PNEUMOSTEM® Treatment in Premature Infants With Bronchopulmonary Dysplasia

Conditions
-----------------
Bronchopulmonary Dysplasia

Intervention / Treatment
-----------------
* Biological: Human Umbilical Cord Blood Derived-Mesenchymal Stem Cells


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Birth weight range: 500g 1250g Fetal gestational age: 23 weeks to 29 weeks Premature infants who cannot do spontaneous breathing, which ventilation rate is less than 12 breaths per min of ventilation rate and 25% of oxygen demand Premature infants who does not improve the breathing or worse within 24 hours prior to enrollment of this study Written consent form signed by a legal representative or a parent Exclusion Criteria: Cyanotic or acyanotic congenital heart diseases except patent ductus arteriosus Severe lung malformation (i.e. Pulmonary hypoplasia, congenital diaphragmatic hernia, congenital cystic lung disease) Severe lung malformation with chromosome anomalies (i.e. Edward syndrome, Patau syndrome, Down syndrome, etc) or severe congenital malformation (Hydrocephalus, Encephalocele, etc) Severe congenital infection (i.e. Herpes, Toxoplasmosis, Rubella, Syphilis, AIDS, etc) CRP > 30 mg/dL; Severe sepsis or shock Premature infants who is going to or expected to have surgery 72 hours before/after this study drug administration Surfactant administration within 24 hours prior to this study drug administration Severe intracranial hemorrhage ≥ grade 3 or 4 Premature infants who have active pulmonary hemorrhage or active air leak syndrome at the time point of screening History of other clinical studies as a participant Premature infants who are allergic to Gentamicin Premature infants who is considered inappropriate by the investigators

Ages Eligible for Study
-----------------
Minimum Age: 5 Days
Maximum Age: 14 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PNEUMOSTEM®<br> | Biological: Human Umbilical Cord Blood Derived-Mesenchymal Stem Cells<br>* Dose A - 10 million cells per kg Dose B - 20 million cells per kg Single intratracheal administration<br>* Other names: PNEUMOSTEM®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participant with adverse reaction | Number of paitents with normal rage of vital signs and laboratory examination Chest x-ray result, Duration of ventilator dependence, Duration of CPAP treatment, Duration of intubation, Occurrence of pneumothorax, Occurrence of intraventricular hemorrhage, Postnatal steroid use (%), Dose of surfactant (%) Cumulative duration of oxygen use | 12 weeks from the day of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of BPD at 36 Week's postmenstrual age | Incidence of BPD at 36 Week's postmenstrual age (PMA)and 28 week's PMA Survival rate at 28 days after birth and 36 week's PMA | 36 week's postmenstrual age | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Human Umbilical Cord Blood Derived Mesenchymal Stem Cells, Bronchopulmonary dysplasia, Premature infants