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

A Safety Study of Intravenous Infusion of Bone Marrow Mesenchymal Stem Cell-derived Extracellular Vesicles (UNEX-42) in Preterm Neonates at High Risk for Bronchopulmonary Dysplasia

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).

Study Overview

• Status: Terminated
• Conditions: Bronchopulmonary Dysplasia
• Intervention / Treatment: Biological: UNEX-42; Biological: Phosphate-buffered saline

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 days to 2 weeks (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Infant whose postnatal age was 3 to 14 days
2. 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)
3. Endotracheally intubated and receiving mechanical ventilation at the time of Screening and randomization.
4. Not expected to be extubated within the next 24 hours after randomization.
5. The subject had a parent/guardian who gave written informed consent.

Exclusion Criteria:

1. Had a congenital heart defect, except for PDA, atrial septal defect or a small/moderate, restrictive ventricular septal defect.
2. Had a serious malformation of the lung, such as pulmonary hypoplasia/aplasia, congenital diaphragmatic hernia, or any other congenital lung anomaly.
3. Was being treated with inhaled nitric oxide.
4. 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).
5. Had a known severe congenital infectious disease (ie, herpes, toxoplasmosis rubella, syphilis, human immunodeficiency virus, cytomegalovirus, etc).
6. High clinical suspicion of active systemic infection, severe sepsis, or septic shock during Screening.
7. 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.
8. Had a Grade 3 or 4 intracranial hemorrhage.
9. Had active pulmonary hemorrhage.
10. The subject was currently participating in any other interventional clinical study.
11. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 20 pmol phospholipid/kg body weight; UNEX-42 administered at 20 pmol phospholipid/kg body weight	Biological: UNEX-42; UNEX-42 is a preparation of extracellular vesicles that are secreted from human bone marrow-derived mesenchymal stem cells suspended in phosphate-buffered saline.
EXPERIMENTAL: 60 pmol phospholipid/kg body weight; UNEX-42 administered at 60 pmol phospholipid/kg body weight	Biological: UNEX-42; UNEX-42 is a preparation of extracellular vesicles that are secreted from human bone marrow-derived mesenchymal stem cells suspended in phosphate-buffered saline.
EXPERIMENTAL: 200 pmol phospholipid/kg body weight; UNEX-42 administered at 200 pmol phospholipid/kg body weight	Biological: UNEX-42; UNEX-42 is a preparation of extracellular vesicles that are secreted from human bone marrow-derived mesenchymal stem cells suspended in phosphate-buffered saline.
PLACEBO_COMPARATOR: Placebo; Phosphate-buffered saline	Biological: Phosphate-buffered saline; Phosphate-buffered saline; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Treatment-emergent Adverse Events During the Post-treatment Phase (Safety and Tolerability)	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.	From Day 1 to 40 Weeks Post-menstrual Age or Hospital Discharge, whichever came first

Collaborators and Investigators

• Sponsor: United Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 9, 2019
• Primary Completion (ACTUAL): May 20, 2021
• Study Completion (ACTUAL): May 20, 2021

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: February 27, 2019
• First Posted (ACTUAL): February 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2021
• Last Update Submitted That Met QC Criteria: September 15, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Bronchopulmonary Dysplasia; Preterm Neonates; Mesenchymal Stem Cell-derived Extracellular Vesicles
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia
• Other Study ID Numbers: UNX-BP-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No