Treatment of Idiopathic Pulmonary Fibrosis(IPF) by REGEND001

Study Overview
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Brief Summary
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Idiopathic pulmonary fibrosis (IPF) is a serious chronic (long term) disease with injury of lung tissues. REGEND001 Autologous Therapy Product, made from bronchial basal cells with ability to regenerate lung tissue, is promising to IPF treatment. In this study, a single-armed clinical trial is ongoing to assess the safety and tolerability of REGEND001 Autologous Therapy Product in treatment of IPF. Different doses of REGEND001 Autologous Therapy Product is evaluated to establish a dose-response relationship and to recommend appropriate dose for subsequent clinical trials.

Official Title
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An Open-labelled Clinical Study to Explore the Safety, Tolerability and Preliminary Efficacy of REGEND001 Autologous Therapy Product for Treatment of Idiopathic Pulmonary Fibrosis (IPF).

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: REGEND001 Autologous Therapy Product


Participation Criteria
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Eligibility Criteria
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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) and more than 50% of the predicted value in forced vital capacity (FVC) 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 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 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
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGEND001 autologous bronchial basal cells<br>Transplantation of autologous bronchial basal cells | Drug: REGEND001 Autologous Therapy Product<br>* Transplantation of REGEND001 Autologous Therapy Product for dosage re-escalation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of the cell therapy-related adverse events (AEs) | Dose escalation is based on incidence of cell therapy-related AEs. Severity of cell therapy-related adverse events (AEs) is evaluated according to Common Terminology Criteria for Adverse Events (CTCAE). | Within 24 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of complication related to bronchoscopy | REGEND001 Autologous Therapy Product is given to subjects by bronchoscopy. Thus, incidence of complication related to bronchoscopy is adapted to assess the safety of the products. | Within 24 weeks after treatment | 
| Change of lung diffusing capacity for single-breath carbon monoxide (DLCO-sb) from baseline | DLCO-sb is measured by the single-breath method. It is considered a measure of the conductance of CO across the alveolar-capillary membrane and its binding with hemoglobin. | 4, 12, and 24 weeks after treatment | 
| Change of forced vital capacity (FVC) from baseline | FVC indicates the volume of air that can forcibly be blown out after full inspiration. | 4 weeks after treatment, 12 weeks after treatment and 24 weeks after treatment | 
| Change of the ratio of diffusing capacity for carbon monoxide/ the alveolar volume (DLCO/VA) from baseline | The DLCO test refers to the diffusing capacity for carbon monoxide in the lungs. It's a type of pulmonary function test that helps to assess how well gas is exchanged between the lungs and the bloodstream.Since DLCO is affected by the amount of inhaled gas and lung volume, the subject's alveolar ventilation (VA) should be considered when evaluating diffusion function to exclude the effect of lung volume on diffusion volume. | 4 weeks after treatment, 12 weeks after treatment and 24 weeks after treatment | 
| Change of 6-minute-walk test (6MWT) from baseline | The 6MWT is a commonly used test for the objective assessment of functional exercise capacity by testing the distance patients can walk at the fastest speed within 6 minutes. | 4 weeks after treatment, 12 weeks after treatment, and 24 weeks after treatment | 
| Change of St. George's respiratory questionnaire (SGRQ) scale from baseline | Quality of life was assessed by St. George's respiratory questionnaire (SGRQ) scale. Total score, ranged from 0 to 100, is the sum of points from all items. A higher value represents a worse outcome. | 4 weeks after treatment, 12 weeks after treatment, and 24 weeks after treatment | 
| Change of 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 after treatment | 
| Idiopathic pulmonary fibrosis (IPF) exacerbation events | Frequency and severity of IPF exacerbation events will be evaluated. | Within 24 weeks after treatment | 
| Blood routine | Number of cases of participants with abnormal laboratory test results. | Within 24 weeks after treatment. | 
| Urine routine | Number of cases of participants with abnormal laboratory test results. | Within 24 weeks after treatment. | 
| Blood biochemistry | Number of cases of participants with abnormal laboratory test results. | Within 24 weeks after treatment | 
| 12-lead Electrocardiogram (ECG) | Number of cases of participants with abnormal 12-lead Electrocardiogram (ECG) | Within 24 weeks after treatment | 
| Carcinoembryonic antigen (CEA) | CEA is a tumor marker used for early diagnosis of lung cancer. | Baseline, 12 weeks after treatment, 24 weeks after treatment | 
| Neuron-specific enolase (NSE) | NSE is a tumor marker significantly elevated in small cell lung cancer. | Baseline, 12 weeks after treatment, 24 weeks after treatment | 
| Cytokeratin-19-fragment (CYFRA21-1) | CYFRA21-1 is a tumor marker which has important value for the pathological classification and prognosis evaluation of lung cancer. | Baseline, 12 weeks after treatment, 24 weeks after treatment | 
| Squamous cell carcinoma antigen (SCC) | SCC is a specific marker for lung squamous cell carcinoma.Tumor markers are monitored to assess the safety. | Baseline, 12 weeks after treatment, 24 weeks after treatment |