Overview

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.

Eligibility

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.