A Safety Study of IV Stem Cell-derived Extracellular Vesicles (UNEX-42) in Preterm Neonates at High Risk for BPD

Phase 1

Terminated

Conditions: Bronchopulmonary Dysplasia

Interventions: Biological: UNEX-42
Biological: Phosphate-buffered saline

Registration Number: NCT03857841

Lead Sponsor: United Therapeutics

Brief Summary: A multicenter, placebo-controlled, randomized, dose escalation, safety, and tolerability study of UNEX-42 in infants born at \<27 weeks of gestational age (GA) at high risk for bronchopulmonary dysplasia (BPD).

Detailed Description: The study was discontinued by the Sponsor on 24 February 2021 due to a business decision, not related to reasons of safety or efficacy. Only data listings were created; no summary or inferential analyses were performed.

Subjects were assessed during Screening and Baseline (prior to randomization) for eligibility in the study. Subjects then received a single IV dose of UNEX-42 at 20 pmol phospholipid/kg body weight, or placebo. After randomization, subjects were monitored in the hospital through 40 Weeks postmentrual age (PMA) or the time of hospital discharge (whichever came first).

The following efficacy and safety assessments occurred during the course of the study:

Efficacy Assessments: incidence and severity of BPD, duration of hospitalization, duration of mechanical ventilation, duration of supplemental oxygen therapy, duration of postnatal steroids, tracheal aspirate inflammatory biomarkers, and Respiratory Severity Score.

Safety Assessments: physical examination, vital signs, adverse events, predefined complications of prematurity, clinical laboratory parameters, and chest x-ray.

Dose administration for Cohort 1 occurred so that there was an observational period of 3 days between dosing the first, second, and third subject to assure the opportunity for safety assessments in at least 1 subject on active treatment. In addition, enrollment between cohorts was to be paused for data review by a Data Monitoring Committee to evaluate the data available after each of the first 2 cohorts were enrolled.

Subjects that completed the Post-treatment Phase (including those that were discharged from the hospital prior to 40 Weeks PMA) continued into the Long-term Outcome Phase and were assessed through 1 year of corrected age.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

Inclusion Criteria

Infant whose postnatal age was 3 to 14 days
Subjects met the following oxygen and birth weight criteria based on gestational age: 23 weeks to 24 weeks 6 days (any birth weight, any oxygen requirement) or 25 weeks to 26 weeks 6 days (fraction of inspired oxygen [FiO2] ≥35% [sustained for >2 hours] at any point during postnatal Days 1 to 14 AND birth weight ≤750 g)
Endotracheally intubated and receiving mechanical ventilation at the time of Screening and randomization.
Not expected to be extubated within the next 24 hours after randomization.
The subject had a parent/guardian who gave written informed consent.

Exclusion Criteria

Had a congenital heart defect, except for PDA, atrial septal defect or a small/moderate, restrictive ventricular septal defect.
Had a serious malformation of the lung, such as pulmonary hypoplasia/aplasia, congenital diaphragmatic hernia, or any other congenital lung anomaly.
Was being treated with inhaled nitric oxide.
Had a known chromosomal abnormality (eg, Trisomy 18, Trisomy 13, or Trisomy 21) or a severe congenital malformation (eg, hydrocephalus and encephalocele, trachea-esophageal fistula, abdominal wall defects, and major renal anomalies).
Had a known severe congenital infectious disease (ie, herpes, toxoplasmosis rubella, syphilis, human immunodeficiency virus, cytomegalovirus, etc).
High clinical suspicion of active systemic infection, severe sepsis, or septic shock during Screening.
Underwent a surgical procedure (requiring admission to an operating room) within 72 hours before randomization or who was anticipated to have a surgical procedure (requiring admission to an operating room) within 72 hours before or following randomization.
Had a Grade 3 or 4 intracranial hemorrhage.
Had active pulmonary hemorrhage.
The subject was currently participating in any other interventional clinical study.
The subject was, in the opinion of the Investigator, so ill that death was inevitable, or was considered inappropriate for the study for any reason(s) other than those listed above.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
60 pmol phospholipid/kg body weight	UNEX-42	UNEX-42 administered at 60 pmol phospholipid/kg body weight
200 pmol phospholipid/kg body weight	UNEX-42	UNEX-42 administered at 200 pmol phospholipid/kg body weight
20 pmol phospholipid/kg body weight	UNEX-42	UNEX-42 administered at 20 pmol phospholipid/kg body weight
Placebo	Phosphate-buffered saline	Phosphate-buffered saline

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Treatment-emergent Adverse Events During the Post-treatment Phase (Safety and Tolerability)	From Day 1 to 40 Weeks Post-menstrual Age or Hospital Discharge, whichever came first	The safety and tolerability of UNEX-42 in subjects with BPD was evaluated by the number of subjects with treatment-emergent adverse events, including death, computed by dose cohort and overall during the Post-treatment Phase.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (6): University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
University of Colorado Hospital
🇺🇸
Aurora, Colorado, United States
Boston Children's Hospital
🇺🇸
Boston, Massachusetts, United States
Children's Mercy Hospital
🇺🇸
Kansas City, Missouri, United States