Treatment of Chronic Obstructive Pulmonary Disease (COPD) With Diffusion Capacity Defect by REGEND001 Cell Therapy

Study Overview
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Brief Summary
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Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide with the characterization of obstructed airflow. In a large number of patients, diffusion function is impaired along with the progression of disease. REGEND001 Autologous Therapy Product, made from bronchial basal cells with ability to regenerate lung tissue, is promising to COPD treatment. In this study, a multicenter, randomized, single-blind, placebo-parallel-controlled trial is performed to assess the efficacy and safety of REGEND001 Autologous Therapy Product in treatment of chronic obstructive pulmonary disease with pulmonary diffusion dysfunction.

Official Title
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A Multicenter, Randomized, Single-Blind, Placebo-Parallel-Controlled Research of REGEND001 Cell Therapy for Treatment of Chronic Obstructive Pulmonary Disease (COPD) With Diffusion Capacity Defect

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: REGEND001 Autologous Therapy Product
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 40 to 80 at the time of screening Diagnosed with COPD for at least 1 year according to the 2021 Global Initiative for Chronic Obstructive Lung Disease (GOLD). At the time of screening, the diffusion function of carbon monoxide (DLCO-sb) is ≥ 20% and < 80% of the predicted value by single-breath method. At the time of screening, the subject has received standardized treatment with GOLD recommended drugs and was in stable condition for ≥ 4 weeks Tolerated for pulmonary function tests Tolerated for bronchoscopy Voluntary to sign the informed consent, and be compliant to complete the procedures and inspections all through the trial. Exclusion Criteria: Female subjects who are pregnant, nursing, or planning to be pregnant after using this product (or male subjects planning to have a pregnant spouse); and participants who did not agree to use a reliable method of contraception within one year from signing informed consent At the time of screening, subject who is positive in each of treponema pallidum antibody (TP-Ab), human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody test. Hepatitis B virus carriers (only HBsAg positive, no hepatitis symptoms and signs, all liver function tests are normal) with stable current condition (deoxyribonucleic acid (DNA) titer is not higher than 500 IU/mL or copy number is less than 1000 copies/mL) can be enrolled. Cured hepatitis C patients with negative result in HCV ribonucleic acid (RNA) test can be enrolled as well. Subject who is assessed to have < 1 year survival time by investigators. Subject with malignant tumors at present or prior to screening. Subject with infections in lung or other sites, requiring intravenous drug treatment within 1 week before screening. Infections are caused by bacteria, virus or others. Subject with two or more exacerbations of moderate to severe COPD and hospitalized by exacerbations within 1 year before screening and led to hospitalization Subject with a history of invasive or noninvasive mechanical ventilation within 4 weeks before screening Subject who has taken prednisone tablets orally and dose ≥ 20 mg/day (or equivalent amount of other oral corticosteroids) within 4 weeks before screening Subject who is assessed to have major lung diseases other than COPD (such as connective tissue disease-related interstitial lung disease, pneumoconiosis, active tuberculosis, primary bronchiectasis, lung cancer, bronchial asthma, severe pulmonary hypertension [>70 mmHg]) by investigators at screening. Subject who has other severe systemic diseases within 6 months before screening or currently, such as diabetes mellitus (glycosylated hemoglobin≥7%), myocardial infarction, unstable angina, congestive heart failure (New York Heart Association [NYHA] class III/IV), stroke, cirrhosis with abnormal liver function (alanine aminotransferase test [ALT], aspartate aminotransferase test [AST] 2.5 times above the upper limit, total bilirubin 1.5 times more than the upper limit of normal), Acute and chronic renal insufficiency (blood creatinine 1.5 times exceeds the upper limit of the normal value), hyperthyroidism, polycythemia vera, etc Subject with deficiency of agranulocytosis (leukocyte < 1.5×10^9/L or neutrophils <0.5×10^9/L), thrombocytopenia (platelet < 100×10^9/L) or severe anemia (hemoglobin<30g/L) at screening. Subject with coagulopathy during the screening period. Subject who has taken anticoagulant therapy and antiplatelet agglutination therapy, such as warfarin, heparin, aspirin, or Plavix within 1 week prior to screening. Subject at risk of suicide or has a history of mental illness or epilepsy at the time of screening. Subject who has severe arrhythmias (such as ventricular tachycardia, supraventricular tachycardia, atrial fibrillation, atrial flutter, etc.) or degree II and above heart conduct abnormalities in 12-lead ECG test at screening. Subject who has a history of alcohol abuse (drinking more than 14 units of alcohol per week [1 unit of alcohol = 360 mL of beer or 45 mL of spirits or 150 mL of wine] within 1 year prior to screening) or illicit drug abuse Subject allergic to cattle products Subject participated in other clinical trials within 3 months prior to screening Investigators, co-investigators, research coordinators, employees of research participants or research centers, or their family members. Any circumstances that the investigator believes may increase the risk to the patient or interfere with the clinical trial.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGEND001 Autologous Therapy Product<br>Transplantation of REGEND001 Autologous Therapy Product | Drug: REGEND001 Autologous Therapy Product<br>* Transplantation of Autologous Therapy Product by<br>|
| Placebo Comparator: Placebo<br>Transplantation of Placebo | Drug: Placebo<br>* Transplantation of Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR) rate of diffusing capacity of the lung for carbon monoxide (DLCO) | Complete response is defined as a ≥10% increase in lung carbon oxide diffusion function (DLCO-sb) from baseline. DLCO-sb is measured by the single-breath method. | 12 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Change of arterial oxygen partial pressure (PaO2) from baseline | PaO2 is a measurement of oxygen pressure in arterial blood. Change of PaO2 reflects increase or decrease of oxygen exchange from lungs to blood. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Change of blood oxygen saturation (SpO2) from baseline | SpO2 relative to baseline is a measure of how much oxygen is in the blood. Change of SpO2 reflects increase or decrease of oxygen exchange from lungs to blood. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Change of images of lung by high resolution computed tomography (HR-CT) from baseline | HR-CT images of lung will be analyzed to indicate the change of pulmonary structure. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Forced vital capacity（FVC） | FVC is the full amount of air that can be exhaled with effort in a complete breath. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Forced expiratory volume in one second (FEV1) | FEV1 is the volume of breath exhaled with effort in one second. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| The ratio of Forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) | The FEV1/FVC is a ratio that reflects the amount of air you can forcefully exhale from your lungs. It's measured by spirometry, a test used to evaluate lung function. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| The ratio of the diffusing capacity for carbon monoxide/ the alveolar volume (DLCO/VA) | 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. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 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. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 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. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Change of modified medical research council (mMRC) chronic dyspnea scale from baseline | It is a questionnaire in which patient has to understand the activity when he feels dyspnoea and based on that patient has to grade the dyspnoea, mMRC results are divided into 0-4 grades according to the degree of activity of the patient when the patient has shortness of breath, and grade 4 indicates that the patient has difficulty breathing at the slightest activity. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Change of chronic obstructive pulmonary disease Assessment Test（CAT）from baseline | The COPD Assessment Test (CAT) is a questionnaire for people with COPD. It is designed to measure the impact of COPD on a person's life, and how this changes over time. The CAT scale includes a total of 8 items, 0 5 points for each item. The total score ranges 0 40 points. Score of 0-10 points indicates slight impact; Score of 11-20 points indicates medium impact: Score of 21-30 points indicates serious impact; Score of 31-40 points indicates very serious impact. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Time to first COPD exacerbation | Exacerbations, are a worsening of COPD symptoms, and frequent exacerbations indicate a deterioration and progression of the disease. A longer time to exacerbations means improvement of disease. | 48 weeks after treatment | 
| Annual frequency of exacerbations | Frequency of exacerbations all through the year. A lower frequency means improvement of disease. | 1 year after treatment | 
| Temperature | Number of cases with abnormal physical examination findings. | Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Breathing | Number of cases with abnormal physical examination findings. | Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Pulse | Number of cases with abnormal physical examination findings. | Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Blood pressure | Number of cases with abnormal physical examination findings. | Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Symptoms, physical examination | Number of cases with abnormal physical examination findings. | Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| 12-lead ECG | Number of cases with abnormal 12-lead Electrocardiogram (ECG). | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Blood routine | Number of cases with abnormal laboratory test results. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Urine routine | Number of cases of participants with abnormal laboratory test results. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Blood biochemistry | Number of cases of participants with abnormal laboratory test results. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Function of blood clotting | Number of cases of participants with abnormal function of blood clotting. | Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Myocardial enzyme profile | Myocardial enzyme profile is tested for safety assessment. | Baseline, 12 weeks after treatment, 24 weeks after treatment, 48 weeks after treatment | 
| Antibody testing for autoimmune diseases | Antibodies related to autoimmune diseases are tested for safety assessment. | Baseline, 12 weeks after treatment, 48 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, 48 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, 48 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, 48 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, 48 weeks after treatment |