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

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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

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.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Number of Subjects With Treatment-emergent Adverse Events During the Post-treatment Phase (Safety and Tolerability)


Condition

Bronchopulmonary Dysplasia

Intervention

UNEX-42

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

3

Start Date

October 9, 2019

Completion Date

May 20, 2021

Primary Completion Date

May 20, 2021

Eligibility Criteria

        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.
      

Gender

All

Ages

3 Days - 14 Days

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03857841

Organization ID

UNX-BP-101


Responsible Party

Sponsor

Study Sponsor

United Therapeutics


Study Sponsor

, , 


Verification Date

September 2021