A Phase I, Randomized, Blinded and Placebo-controlled Trial to Evaluate the Safety, Tolerability, and Potential Efficacy of Allogeneic Human Mesenchymal Stem Cell Infusion in Patients With Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- To determine the safety and tolerability of intravenous allo hMSCs in patients with Idiopathic Pulmonary Fibrosis (IPF).
研究概览
简要总结
This is a phase I, randomized, blinded, placebo-controlled 9 subjects pilot safety run-in followed by an additional 16 randomized subjects for a total of 25 subjects. In the pilot phase subjects will be randomized into three treatment groups of allogenic mesenchymal stem cells and in the randomized phase subjects will receive either allogenic mesenchymal stem cells or matched placebo.
详细描述
Idiopathic Pulmonary Fibrosis (IPF) is a progressive and debilitating lung disease characterized by interstitial fibrosis with decreasing lung volumes and pulmonary insufficiency eventually resulting in death. Patients with Idiopathic Pulmonary Fibrosis (IPF) typically present with complaints of sub acutely progressive dyspnea and non-productive cough, often accompanied by digital clubbing. Due to the insidious onset of symptoms, however, most patients are diagnosed at late stages of the disease after significant fibrosis has occurred. Physical exam is characterized by hypoxemia, "dry" inspiratory crackles on auscultation, and occasional digital clubbing (6). Pulmonary function tests (PFTs) usually reveal restrictive lung physiology with progressive decline of forced vital capacity (FVC), diffusion capacity (DLCO) and six-minute walk distances. Diagnosis is established by the pathologic finding of usual interstitial pneumonia (with sub epithelial fibroblastic foci) by open lung biopsy (7), and/or by high resolution CT (HRCT) demonstrating the characteristic findings of peripheral/basal sub pleural reticulonodular changes with fibrosis, honeycombing, and traction bronchiectasis (8, 9).
The prognosis for patients with Idiopathic Pulmonary Fibrosis (IPF) is uniformly poor. The natural history of the disease is characterized by inexorable progressive decline interspersed with "exacerbations" or periods of accelerated disease which are often fatal (5). There are no FDA approved treatment options for patients with Idiopathic Pulmonary Fibrosis (IPF) and thus no standard of care. In cases of patients under the age of 60 with limited comorbid disease, lung transplant may be offered. Patients with Idiopathic Pulmonary Fibrosis (IPF) receive empiric treatment, supportive care alone, and more recently, are offered enrollment in clinical trials.
The pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) is characterized by epithelial cell injury and activation with interstitial inflammation, fibroblast proliferation with extracellular matrix collagen deposition, and eventual loss of function. Because mesenchymal stem cells are known to home to sites of injury, inhibit inflammation, and contribute to epithelial tissue repair, their use has been suggested as a novel therapy for the treatment of Idiopathic Pulmonary Fibrosis (IPF).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide written informed consent.
- •Subjects age equal to or greater than 40 and equal to or less than 90 years at the time of signing the Informed Consent Form.
- •Have a clinical diagnosis of Idiopathic Pulmonary Fibrosis (IPF) prior to screening
- •Forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity (DLCO) ≥30% (corrected for hemoglobin but not alveolar volume).
- •RVSP equal to or less than 50 mmHg, as documented by Doppler echo or right heart catheterization.
- •Female subjects must be surgically sterile or post-menopausal (greater than 1 year).
排除标准
- •HRCT and/or surgical lung biopsy results inconsistent with the diagnosis of IPF.
- •Infiltrative lung disease of any type other than Idiopathic Pulmonary Fibrosis (IPF), lungs disease related to fibrogenic agents, toxins, drugs or other exposures, granulomatous lung disease, pulmonary vascular disease, or known connective tissue disease.
- •Inability to perform any of the assessments required for endpoint analysis (report safety or tolerability concerns, perform pulmonary function tests or high resolution CT (HRCT), undergo blood draws, read and respond to questionnaires.
- •Currently receiving (or received within four weeks of screening) any medication, treatment, or experimental agents for the treatment of Idiopathic Pulmonary Fibrosis (IPF), except for patients receiving non drug therapies will include oxygen saturation therapy (oxygen supplementation) and pulmonary rehabilitation.
- •Active listing (or expected future listing) for transplant of any organ.
- •Clinically important abnormal screening laboratory values, including but not limited to: hemoglobin <8 g/dl, white blood cell count <3000/mm3, platelets <80,000/mm3, INR > 1.5, aspartate transaminase, alanine transaminase, or alkaline phosphatase > 3 times upper limit of normal, total bilirubin > 1.5 mg/dl.
- •Serious comorbid illness that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study. Including, but not limited to: HIV, advanced liver or renal failure, class III/IV congestive heart failure, myocardial infarction, unstable angina, or cardiac revascularization within the last six months, or severe obstructive ventilatory defect.
- •Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study.
- •Have known allergies to penicillin or streptomycin.
- •Be an organ transplant recipient.
- •Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively- treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
- •Have a non-pulmonary condition that limits lifespan to less than 1 year.
- •Have a history of drug or alcohol abuse within the past 24 months.
- •Be serum positive for Human immunodeficiency virus (HIV), hepatitis BsAg or Viremic hepatitis C.
- •Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
- •Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female patients must undergo a blood or urine pregnancy test at screening and within 36 hours prior to injection.
- •Female subjects must have a FSH less than 25.8 IU/L
- •Subject with hypersensitivity to dimethyl sulfoxide (DMSO)
- •Saturated oxygen (SpO2 of less than 93% (room air [sea level] at rest). SpO2 of less than 88% (room air [>5,000 feet above sea level (1524 meters) at rest).
结局指标
主要结局
To determine the safety and tolerability of intravenous allo hMSCs in patients with Idiopathic Pulmonary Fibrosis (IPF).
时间窗: One month post infusion
Safety (Primary): Incidence (one month post infusion) of any treatment-emergent serious adverse events (TE-SAEs), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities.
次要结局
- Difference in frequency of acute exacerbations of Idiopathic Pulmonary Fibrosis (IPF)(4 weeks following infusion)
- Death from any cause.(60 weeks.)
- To explore effects of allogenic human mesenchymal stem cells on lung function: Diffusing Capacity (DLCO)(Participants will be followed from 12 weeks to an expected average of 60 weeks following infusion.)
- - To explore effects of allo hMSCs on lung function: forced vital capacity (FVC).(Participants will be followed from 12 weeks to an expected average of 60 weeks following infusion.)
- To explore effects of allogenic human mesenchymal stem cells on symptom related quality of life.(Participants will be followed from 4 weeks to an expected average of 60 weeks following infusion.)
研究者
Joshua M Hare
Chief Science Officer / Director of Interdisciplinary Stem Cell Institute
University of Miami