Safety and Efficacy of MSC-EVs in the Prevention of BPD in Extremely Preterm Infants

Inclusion Criteria:

• From birth up to 10 days chronological age.

• From 23 weeks up to 28 weeks (27 week+6 days) gestational age at birth.

• Birth weight ≥ 500g but ≤1500g.

• Endotracheally intubated and receiving mechanical ventilation with FiO2 > 25%anytime between 3 and 10 days postnatally or needing re-intubation due torespiratory complications, - Not expected to be extubated within the next 24/48hours after enrolment.

• Written informed consent from parents/legally designated representative.

Exclusion Criteria:

• Surfactant administration less than 24 hours prior to (first) IMP administration.

• Has a congenital heart defect, except for patent ductus arteriosus (PDA), atrialseptal defect or a small/moderate, restrictive ventricular septal defect.

• Has a serious malformation of the lung, such as pulmonary hypoplasia/aplasia,congenital diaphragmatic hernia, or any other congenital lung anomaly.

• Being treated with inhaled nitric oxide.

• Has a known chromosomal abnormality (e.g., Trisomy 18, Trisomy 13, or Trisomy 21) ora severe congenital malformation (e.g., hydrocephalus and encephalocele,trachea-oesophageal fistula, abdominal wall defects, and major renal anomalies).

• Has had a known severe congenital infectious disease (i.e., herpes, toxoplasmosisrubella, syphilis, human immunodeficiency virus, cytomegalovirus, etc.).

• Active systemic infection, severe sepsis, or septic shock at Screening up tobaseline (phase I) or randomization (phase II).

• Underwent a surgical procedure (requiring admission to an operating room) within 72hours before baseline (phase I)/randomization (phase II) or who is anticipated tohave a surgical procedure (requiring admission to an operating room) within 72 hoursbefore or following baseline (phase I)/randomization (phase II).

• Has had a Grade 3 or 4 intraventricular haemorrhage (IVH).

• Has active pulmonary haemorrhage.

• Has periventricular leukomalacia (PVL).

• The subject is currently participating in any other interventional clinical study.

• The subject is, in the opinion of the Investigator, so ill that death is inevitable,or is considered inappropriate for the study such as an infant that receivedthoracic compressions and/or adrenaline administration during stabilization in thedelivery room and for any reason(s) other than those listed above.