Clinical trial NCT04255147: Cellular Therapy for Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia
Official title: Helping Underdeveloped Lungs With Cells (HULC): Mesenchymal Stromal Cells in Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia - Phase 1 Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Bronchopulmonary Dysplasia
Keywords: Phase I clinical trial
Stem cells
Mesenchymal stromal cell
Bronchopulmonary Dysplasia
Preterm birth
Cell therapy
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Ontario Institute of Regenerative Medicine (OIRM)
name: Stem Cell Network
First posted: 2020-02-05
Enrollment: 9
Sex: ALL
Minimum age (years): 7
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Detailed description: Complications of extreme preterm birth are the primary cause of mortality in children under the age of five. Bronchopulmonary dysplasia (BPD), the chronic lung disease that follows ventilator and oxygen therapy for acute respiratory failure, is the most common complication of extreme prematurity and contributes to life-long respiratory and neurological impairment. Currently, there is no effective treatment for BPD. The multi-factorial nature of BPD makes it challenging for traditional pharmacological therapies targeting a single pathway to have a major impact on outcome. Mesenchymal stromal cells (MSCs) may provide a promising new treatment avenue due to their pleiotropic effects that may prevent neonatal lung injury while promoting lung (and other organ) growth. A systematic review and meta-analysis of all preclinical studies testing MSCs in neonatal lung injury models provides strong evidence for the lung protective effect of MSCs. Additionally, studies in a large preclinical model of extreme prematurity and chronic lung injury suggest feasibility, safety and short-term hemodynamic benefit of intravenously delivered human umbilical cord tissue-derived MSCs (uc-MSC).

The aim of this study is to establish the safety, maximum feasible dose and feasibility of intravenously delivered allogeneic uc-MSCs in preterm infants at risk of developing BPD. This will be a Phase 1, open-label, single center, dose-escalating trial using a 3+3+3 design.

Eligibility criteria: A participant needs to meet all inclusion criteria between day of life 7-28 to be eligible:

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Occurrence and rate of dose limiting toxicity
timeFrame: Up to 1 week following uc-MSC injection
Secondary outcomes:
measure: Rate of Death
timeFrame: From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first)
measure: Occurrence of Other Severe Complications of Prematurity
timeFrame: From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first)
measure: FiO2 and Oxygen Index
timeFrame: From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)
measure: Need for Ventilatory Support
timeFrame: From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)
measure: Need for Postnatal Steroids
timeFrame: From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)
measure: Incidence and Severity of BPD
timeFrame: From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)
measure: Rate of Survival Without (moderate or severe) BPD
timeFrame: From enrollment until 36 weeks corrected gestational age
measure: Changes in Pulmonary Hemodynamics
timeFrame: At enrollment, 48 hours following uc-MSC injection, 28 days of life, and 36 weeks corrected gestational age
measure: Biological Measure of Clinical Improvement
timeFrame: 72-96 hours following uc-MSC injection
measure: Biological Measure of Lung Improvement
timeFrame: 72-96 hours following uc-MSC injection
measure: Feasibility: Cell Administration
timeFrame: Day of life 7-28
measure: Feasibility: Recruitment Efficiency
timeFrame: Day of life 7-28
measure: Feasibility: Recruitment Timing
timeFrame: Day of life 7-28
measure: Feasibility: Participant Retainment
timeFrame: From enrollment until follow-up at 18-30 months-of-age
measure: Bayley Scale of Infant and Toddler Development
timeFrame: 18-30 months-of-age
measure: Long-term Safety Follow-Up
timeFrame: Ten years following follow-up visit
measure: Animated Information Video
timeFrame: Day of life 7-28
Other outcomes:
Locations:
city: Gloucester
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Bernard Thébaud, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: