Helping Underdeveloped Lungs With Cells (HULC): Mesenchymal Stromal Cells in Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia - Phase 1 Study
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Occurrence and rate of dose limiting toxicity
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 7 Days 至 28 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Mesenchymal Stromal Cell Therapy
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.
干预措施: Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells (Biological)
结局指标
主要结局
Occurrence and rate of dose limiting toxicity
时间窗: Up to 1 week following uc-MSC injection
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.
次要结局
- Need for Postnatal Steroids(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))
- Incidence and Severity of BPD(From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first))
- Rate of Survival Without (moderate or severe) BPD(From enrollment until 36 weeks corrected gestational age)
- Feasibility: Recruitment Timing(Day of life 7-28)
- Changes in Pulmonary Hemodynamics(At enrollment, 48 hours following uc-MSC injection, 28 days of life, and 36 weeks corrected gestational age)
- Biological Measure of Clinical Improvement(72-96 hours following uc-MSC injection)
- Biological Measure of Lung Improvement(72-96 hours following uc-MSC injection)
- Feasibility: Participant Retainment(From enrollment until follow-up at 18-30 months-of-age)
- Bayley Scale of Infant and Toddler Development(18-30 months-of-age)
- Long-term Safety Follow-Up(Ten years following follow-up visit)
- Rate of Death(From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first))
- Feasibility: Cell Administration(Day of life 7-28)
- 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))
- Animated Information Video(Day of life 7-28)
- Feasibility: Recruitment Efficiency(Day of life 7-28)