A Phase I, Randomized Study of the Safety and Efficacy of Intravenous Delivery of Lung Spheroid Stem Cells (LSCs) in Patients With Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Participants With Hematological Parameters of Potential Clinical Importance
研究概览
简要总结
Purpose:
To demonstrate the safety and efficacy of autologous Lung Spheroid Stem Cells (LSCs) administered by intravenous infusion in patients with idiopathic pulmonary fibrosis Progressive Fibrotic Interstitial Lung Disease.
Participants:
Patients with Idiopathic Pulmonary Fibrosis (IPF) and Progressive Fibrotic Interstitial Lung Disease
Procedures (methods):
24 patients previously diagnosed with idiopathic pulmonary fibrosis or Progressive Fibrotic Interstitial Lung Disease meeting all inclusion/exclusion criteria will be evaluated at baseline. LSCs will be grown from autologous trans-bronchial pulmonary biopsy specimens. The first group, consisting of 6 patients will be randomized after completion of the screening procedures to either a treatment group of 100 million LSCs administered via intravenous infusion or to a control group (standard care) in a 2:1 LSC to control group ratio. The second group of 18 patients will be randomized after completion of the screening procedures to either a treatment group of 200 million LSCs administered via intravenous infusion or to a control group (standard care) in a 2:1 LSC to control group ratio. Patients will be randomized using permuted blocks in a 2:1 LSC to control group ratio, providing a distribution of 8:4:12 patients among the control, low dose, and high dose groups, respectively. If the patient is randomized and 100 million LSCs are not achieved, then the patient will be analyzed separately and another patient enrolled. Intravenous infusion of LSCs will take place 4-8 weeks after the pulmonary biopsies are obtained. All patients will be followed up at months 0.5, 1, 3, 6, 9, 12, 18, and 24 after infusion to complete the safety and efficacy assessments listed herein. All patients will receive standard of care for their IPF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female between the ages of 40 to
- •Diagnosis of a Progressive Fibrotic Interstitial Lung Disease
- •Diagnosis of IPF based on the following criteria in accordance with American Thoracic Society (ATS) guidelines for diagnosing IPF:
- •Definite usual interstitial pneumonia (UIP) confirmed on surgical lung biopsy (SLB) with all other etiologies for UIP excluded OR High resolution CT scan (HRCT) showing definite UIP with all other etiologies for UIP excluded.
- •Probable UIP on both imaging and surgical lung biopsy with all other etiologies for UIP excluded.
- •Forced vital capacity (FVC) greater than 50% of predicted with a ratio of forced expiratory volume in 1 second to FVC (FEV1/FVC) greater than 0.75 (Pulmonary function tests must be completed no more than 90 days before screening).
- •Diffusing capacity for carbon monoxide (DLCO) greater than 25% of predicted capacity.
- •Ability to perform a 6-Minute Walk Test (6MWT) at screening.
- •Competency to understand the information given in the Human Research and Ethics Committee (HREC) approved Informed Consent Form and must sign the form prior to the initiation of any study procedures
排除标准
- •Diagnosis of an interstitial lung disease (ILD) or restrictive lung disease other than IPF or Progressive Fibrotic Interstitial Lung Disease.
- •Obstructive lung disease as determined by evidence of airflow obstruction on HRCT or physiologic criteria including: FEV1/FVC ratio less than 0.75, Residual volume (RV) greater than 120% by plethysmography or significant (verified by radiologist) emphysema on HRCT or evidence of reactive airway disease by change in FEV1 of greater than 12% following bronchodilator challenge.
- •Evidence of sustained improvement lung function defined as improvement from pre-therapy pulmonary function tests (PFTs) observed with two or more successive post-therapy PFTs over the year prior to randomization.
- •Active or recent (less than 60 days prior to enrollment) significant respiratory tract infections, or a history of frequent (greater than 2 per year for the last 2 years) infective exacerbations of IPF.
- •Hospitalization within 60 days of screening for an acute exacerbation of IPF (AE-IPF).
- •Chronic heart failure (NYHA class III/IV) or known left ventricular ejection fraction less than 45%.
- •Acute or chronic impairment (other than dyspnea) which limits the ability to comply with study requirements and procedures including the 6MWT.
- •Subject requires hemodialysis, peritoneal dialysis or hemofiltration.
- •Infection with HIV
- •Viral Hepatitis
- •Resting oxygen requirements or >4 L of nasal canula oxygen needed with exertion
研究组 & 干预措施
Low Dose LSCs (cohort 1) n = 4 planned
4-8 weeks following transbronchial biopsy, participants in this arm will receive 100 million Lung Spheroid Stem Cell (LSC) infusion.
干预措施: Lung Spheroid Stem Cells 100 million (Biological)
High Dose LSCs (Cohort 2) n = 12 planned
4-8 weeks following transbronchial biopsy, participants in this arm will receive 200 million LSC infusion.
干预措施: Lung Spheroid Stem Cells 200 million (Biological)
Usual Care (Cohort 1) n = 2 planned
Patients will receive standard of care with no biopsy and no infusion. Placebo will not be used.
Usual Care (Cohort 2) n = 6 planned
Patients will receive standard of care with no biopsy and no infusion. Placebo will not be used.
结局指标
主要结局
Number of Participants With Hematological Parameters of Potential Clinical Importance
时间窗: Through study completion, 24 months
Blood samples will be collected for the assessment of hematology parameters. The clinical concern range for the parameters will be: hematocrit (high: \>0.54 proportion of red blood cells in blood); hemoglobin (high: \>180 grams per liter \[g/L\]), lymphocytes (low: \<0.8x10\^9 cells per liter \[cells/L\]); neutrophil count (low: \<1.5x10\^9 cells/L); platelet count (low: \<100x10\^9 cells/L and high: \>550x10\^9 cells/L); white blood cells count (low: \<3x10\^9 cells/L and high: \>20x10\^9 cells/L).
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Through study completion, 24 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance
时间窗: Through study completion, 24 months
Blood samples will be collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters are: albumin (low: \<30 millimoles per liter \[mmol/L\]); alanine aminotransferase (ALT) (high: \>=2xupper limit of normal \[ULN\]); aspartate aminotransferase (AST) (high: \>=2xULN); alkaline phosphatase (ALP) (high: \>=2xULN); total bilirubin (high: \>=1.5xULN); calcium (low: \<2 mmol/L and high: \>2.75 mmol/L); glucose (low: \<3 mmol/L and high: \>9 mmol/L); potassium (low: \<3 mmol/L and high: \>5.5 mmol/L) and sodium (low: \<130 mmol/L and high: \>150 mmol/L).
次要结局
- Change from baseline in Forced Vital Capacity (FVC)(screening visit prior to infusion and 360days post infusion)
- Change from baseline in 6 minute walk test distance (meters)(screening visit prior to infusion and 360days post infusion)
- Change from Baseline in High Resolution CT scan Fibrosis Score (0-50)(screening visit prior to infusion and 12 months after infusion)
- Change from baseline in Diffusion capacity of the lung for carbon monoxide (DLCO)(screening visit prior to infusion and 360days post infusion)