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

NCT ID: NCT03857841

Last Updated: 2021-10-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-09
• Study Completion Date: 2021-05-20

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.

Conditions

Bronchopulmonary Dysplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

20 pmol phospholipid/kg body weight

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

Group Type: EXPERIMENTAL

UNEX-42

Intervention Type: BIOLOGICAL

UNEX-42 is a preparation of extracellular vesicles that are secreted from human bone marrow-derived mesenchymal stem cells suspended in phosphate-buffered saline.

60 pmol phospholipid/kg body weight

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

Group Type: EXPERIMENTAL

UNEX-42

Intervention Type: BIOLOGICAL

UNEX-42 is a preparation of extracellular vesicles that are secreted from human bone marrow-derived mesenchymal stem cells suspended in phosphate-buffered saline.

200 pmol phospholipid/kg body weight

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

Group Type: EXPERIMENTAL

UNEX-42

Intervention Type: BIOLOGICAL

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

Phosphate-buffered saline

Group Type: PLACEBO_COMPARATOR

Phosphate-buffered saline

Intervention Type: BIOLOGICAL

Phosphate-buffered saline

Interventions

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.

Intervention Type: BIOLOGICAL

Phosphate-buffered saline

Phosphate-buffered saline

Intervention Type: BIOLOGICAL

Other Intervention Names

Placebo

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.

• Minimum Eligible Age: 3 Days
• Maximum Eligible Age: 14 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Colorado Hospital

Aurora, Colorado, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

UNX-BP-101

Identifier Type: -

Identifier Source: org_study_id