Clinical Efficacy and Safety of Autologous Lung Stem Cell Transplantation in Patients With Idiopathic Pulmonary Fibrosis

Study Overview
=================
Brief Summary
-----------------
Idiopathic pulmonary fibrosis (IPF) is a chronic and ultimately fatal disease characterized by a progressive damage of lung structure and decline in lung function.This study intends to carry out an open, single-center, non-randomized, self control phase I clinical trial. During the treatment, lung stem cells will be isolated from patients' own bronchi and expanded in vitro. Cultured cells will be injected directly into the lesion by fiberoptic bronchoscopy after lavage. After 24-week observation, the investigators will evaluate the safety and efficacy of the treatment by measuring the key clinical indicators.

Official Title
-----------------
Clinical Efficacy and Safety of Autologous Lung Stem Cell Transplantation in Patients With Idiopathic Pulmonary Fibrosis

Conditions
-----------------
Idiopathic Pulmonary Fibrosis

Intervention / Treatment
-----------------
* Biological: Lung stem cells


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, aged between 50 to 75; Subjects diagnosed with IPF according to guidelines for the diagnosis of idiopathic pulmonary fibrosis 2018 edition; Subjects with 30% 79% of the predicted value in diffusing capacity for carbon monoxide (DLCO) in pulmonary function tests 3 months before screening; Subjects with typical High-resolution computed tomography (HR-CT) imaging findings of idiopathic pulmonary fibrosis in the past 12 months; Subjects tolerant to bronchofiberscope; Subjects fully informed of the purpose, method and possible discomfort of the trial, agreeing to participate in the test, and voluntarily signing the informed consent; Subjects with good adherence, willingness to take medication and regular follow-up examinations as required by the protocol; Subjects able to understand and cooperate with the completion of pulmonary function tests. Exclusion Criteria: Subjects who cannot tolerate cell therapy; Pregnant or lactating women; Subjects with syphilis or any of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) positive antibody; Of which stable HBV carriers after drug treatment (DNA titer ≤500 IU/mL or copy number <1000 copies/mL) and cured hepatitis C patients (HCV RNA is negative) can be enrolled; Subjects with malignant tumors or a history of malignant tumors; Subjects with serious significant pulmonary infection and needing anti-infection treatment; Subjects with taking drugs which caused lung fibroblast such as amiodarone in a long term before screening; Subjects with infections in lung or other site, including bacterial and viral infections, requiring intravenous treatment before cell transplantation; Subjects with a history of invasive or noninvasive mechanical ventilation within 4 weeks; Subjects with any of the following lung diseases: asthma, active tuberculosis, pulmonary embolism, pneumothorax, pulmonary hypertension, pneumoconiosis, etc.; lung cancer, bronchiolitis obliterans or other active lung disease; Pneumonia currently or within the last 4 weeks; Pneumonectomy Previously; Subjects needing oxygen therapy currently (oxygen therapy time> 15h/d); Subjects suffering from serious other systemic diseases, such as myocardial infarction, unstable angina, liver cirrhosis, acute glomerulonephritis, connective tissue disease, etc.; Subjects with following results : leukopenia (leukopenia < 4×10^9/L) or agranulocytosis (leukocyte < 1.5×10^9/L or neutrophils < 0.5×10^9/L) of any cause; Blood creatinine > 2.5 times the upper limit of normal; Alanine transaminase (ALT) and Aspartate transaminase (AST) > 2.5 times the upper limit of normal values in the laboratory tests; Subjects with a history of mental illness or suicide risk, epilepsy or other central nervous system disorders; Subjects with severe arrhythmias (such as ventricular tachycardia, frequent supraventricular tachycardia, atrial fibrillation, atrial flutter, etc.) or atrioventricular block of degree II or above, shown by 12-lead Electrocardiogram (ECG); Subjects with a history of abusing alcohol and illicit drug; Subjects with serious heart disease [New York Heart Association (NYHA) class III-IV]; Subjects who are allergic to cattle products; Subjects who participated in other clinical trials in the past 3 months; Subjects with poor compliance and difficult to complete the investigation; Investigators, employees of research centers or family members of them (none of whom are suitable to participate in the trial to ensure the objectivity of the research); Subjects who had an acute exacerbation of IPF or hospitalized for other respiratory diseases 3 or more times in the past 1 year; Subjects who take nintedanib for medication within 1 month, or plan to continue taking nintedanib for medication; Subjects with other acquired or congenital immunodeficiency disorders, or with a history of organ transplantation or cell transplant therapy; Subjects whose expected survival may be less than one year judged by the investigator; Male participants of childbearing potential and female participants within childbearing age were reluctant to use effective contraception from the time of signing the informed consent to 6 months after cell therapy; Subjects assessed as inappropriate to participate in this clinical trial by investigator.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lung stem cells<br>Patients will receive 0.5-5x10^6 (0.5-5 million)/Kg/person cells of clinical grade lung stem cells (LSCs)injected via fiberoptic bronchoscopy after fully lavage of the localized lesions. | Biological: Lung stem cells<br>* Patients will receive 0.5-5x10^6 (0.5-5 million) /Kg/person cells of clinical grade lung stem cells (LSCs) injected via fiberoptic bronchoscopy after fully lavage of the localized lesions.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome of the study was the incidence and severity of the cell therapy-related AEs | To evaluate the safety of the drugs | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of complication related to bronchoscopy |  | 1 week | 
| Evaluation of cell therapy efficacy through DLCO-SB test |  | 24 weeks | 
| exercise tolerance test (6MWD) |  | 24 weeks | 
| Life quality: assessed by St. George respiratory questionnaire (SGRQ) |  | 24 weeks | 
| Change from baseline in forced vital capacity (FVC) | FVC indicates the volume of air that can forcibly be blown out after full inspiration. | 24 weeks | 
| Change from baseline in imaging of lung by high resolution computed tomography (HR-CT) | Images of lung will be analyzed to indicate the newly-derived pulmonary structure | 24 weeks | 
| IPF exacerbation events |  | 24 weeks | 
| Change from baseline in forced expiratory volume in one second (FEV1) | FEV1 is the volume of breath exhaled with effort in one second. | 24 weeks |