Cellular Therapy for Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia

NCT04255147 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: HULC-1
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

Bronchopulmonary dysplasia (BPD) is a common and chronic lung disease that occurs in preterm infants following ventilator and oxygen therapy and is associated with long-term health consequences. Preclinical research shows that mesenchymal stromal cells (MSCs) can modify a number of pathophysiological processes that are central to the progression of BPD and thus present as a promising new treatment option. The main purpose of this Phase I study is to evaluate the safety of human umbilical cord tissue-derived MSCs in extremely preterm infants at risk of developing BPD.

Conditions

Bronchopulmonary Dysplasia

Keywords

Phase I clinical trial; Stem cells; Mesenchymal stromal cell; Bronchopulmonary Dysplasia; Preterm birth; Cell therapy

Outcome Measures

Primary Outcomes (1)

• Occurrence and rate of dose limiting toxicity

  Dose limiting toxicity consists of the following events: * Death occurring within 24 hours of injection; * Pulmonary embolism defined as acute increase in right ventricular afterload (identified by serial targeted neonatal echocardiography) and signs of acute increased dead space ventilation (respiratory distress, increased PaCO2, increased minute ventilation) occurring within 24 hours of injection; * Hypersensitivity / anaphylactic to uc-MSCs defined as any severe systemic inflammatory response syndrome with negative blood culture not consistent with the overall clinical course of the infant occurring within 72 hours of injection; * Any other serious adverse event not expected in this patient population for which there is no alternative explanation but the administration of uc-MSCs, occurring within 1 week of injection.

  Up to 1 week following uc-MSC injection

Secondary Outcomes (17)

• Rate of Death

  From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first)

• Occurrence of Other Severe Complications of Prematurity

  From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first)

• FiO2 and Oxygen Index

  From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)

• Need for Ventilatory Support

  From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)

• Need for Postnatal Steroids

  From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)

Study Arms (1)

Mesenchymal Stromal Cell Therapy

EXPERIMENTAL

Patients are enrolled into one of three escalating dose panels based on the time of enrolment. The first three patients will receive 1 million cells/kg of body weight, the next three patients will receive 3 million cells/kg of body weight, and the final three patients will receive 10 million cells/kg of body weight. Progression through the escalating dose panels is subject to review by an independent Data Safety Monitoring Committee.

Biological: Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells

Interventions

Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells BIOLOGICAL

Cryopreserved allogeneic umbilical cord tissue-derived mesenchymal stromal cells are thawed and administered intravenously.

Mesenchymal Stromal Cell Therapy

Eligibility Criteria

• Age: 7 Days - 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Admission to The Ottawa Hospital (TOH) NICU - General Campus or Sunnybrook Health Sciences Centre NICU
• Gestational age at birth \< 28 weeks
• Intubated on mechanical ventilation
• Fraction of inspired oxygen ≥ 30%
• Parents or substitute decision make must provide written informed consent

You may not qualify if:

• Severe congenital anomaly by antenatal ultrasound and physical examination
• Ongoing shock and severe sepsis (confirmed by positive blood or cerebrospinal fluid culture) as per attending physician
• Severe pulmonary hemorrhage
• Active pneumothorax (with chest tube in-situ)
• Hemodynamically significant PDA
• Participants with caregiver unable to speak English or French
• Patient i moribund, not expected to survive
• Planned to be extubated in the 24 hours after uc-MSC administration

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Ontario Institute of Regenerative Medicine (OIRM): collaborator
• Stem Cell Network: collaborator

Study Sites (2)

The Ottawa Hospital - General Campus

Gloucester, Ontario, K1T 8L6, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Premature Birth

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Bernard Thébaud, MD, PhD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: February 5, 2020
• Study Start: October 17, 2022
• Primary Completion: November 6, 2023
• Study Completion (Estimated): November 6, 2033
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)