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

Primary Purpose

Bronchopulmonary Dysplasia

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
UNEX-42
Phosphate-buffered saline
Sponsored by
United Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bronchopulmonary Dysplasia focused on measuring Bronchopulmonary Dysplasia, Mesenchymal Stem Cell-derived Extracellular Vesicles, Preterm Neonates

Eligibility Criteria

3 Days - 14 Days (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Colorado Hospital
  • Boston Children's Hospital
  • Brigham and Women's Hospital
  • Beth Israel Deaconess Medical Center
  • University of Mississippi Medical Center
  • Children's Mercy Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

20 pmol phospholipid/kg body weight

60 pmol phospholipid/kg body weight

200 pmol phospholipid/kg body weight

Placebo

Arm Description

UNEX-42 administered at 20 pmol phospholipid/kg body weight

UNEX-42 administered at 60 pmol phospholipid/kg body weight

UNEX-42 administered at 200 pmol phospholipid/kg body weight

Phosphate-buffered saline

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
February 20, 2019
Last Updated
September 15, 2021
Sponsor
United Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT03857841
Brief Title
A Safety Study of IV Stem Cell-derived Extracellular Vesicles (UNEX-42) in Preterm Neonates at High Risk for BPD
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Terminated
Why Stopped
The study was discontinued due to a business decision; no safety concerns were noted.
Study Start Date
October 9, 2019 (Actual)
Primary Completion Date
May 20, 2021 (Actual)
Study Completion Date
May 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
United Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchopulmonary Dysplasia
Keywords
Bronchopulmonary Dysplasia, Mesenchymal Stem Cell-derived Extracellular Vesicles, Preterm Neonates

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
20 pmol phospholipid/kg body weight
Arm Type
Experimental
Arm Description
UNEX-42 administered at 20 pmol phospholipid/kg body weight
Arm Title
60 pmol phospholipid/kg body weight
Arm Type
Experimental
Arm Description
UNEX-42 administered at 60 pmol phospholipid/kg body weight
Arm Title
200 pmol phospholipid/kg body weight
Arm Type
Experimental
Arm Description
UNEX-42 administered at 200 pmol phospholipid/kg body weight
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Phosphate-buffered saline
Intervention Type
Biological
Intervention Name(s)
UNEX-42
Intervention Description
UNEX-42 is a preparation of extracellular vesicles that are secreted from human bone marrow-derived mesenchymal stem cells suspended in phosphate-buffered saline.
Intervention Type
Biological
Intervention Name(s)
Phosphate-buffered saline
Other Intervention Name(s)
Placebo
Intervention Description
Phosphate-buffered saline
Primary Outcome Measure Information:
Title
Number of Subjects With Treatment-emergent Adverse Events During the Post-treatment Phase (Safety and Tolerability)
Description
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.
Time Frame
From Day 1 to 40 Weeks Post-menstrual Age or Hospital Discharge, whichever came first

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Days
Maximum Age & Unit of Time
14 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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