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

Regend Therapeutics58 enrolled

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 cell therapy, comprised of airway 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 cell therapy in treatment of chronic obstructive pulmonary disease with diffusion capacity defect.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Chronic Obstructive Pulmonary Disease

Interventions

Eligibility

Sex: ALLMin age: 40 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female, aged 40 to 75 at the time of signing informed consent. * Diagnosed with COPD according to the 2021 Global Initiative for Chronic Obstructive Lung Disease (GOLD). * The ratio of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)FEV1/FVC is \< 70% after inhalation of bronchodilators. * The diffusion function of carbon monoxide (DLCO) is ≥ 20% and \< 80% of the predicted value at screening. * Tolerated to pulmonary function tests. * Tolerated to bronchoscopy * Voluntary to sign the informed consent, coordinated to finish the trial-related procedures and tests, and capable of recording or stating the change of disease condition in a relatively complete manner. Exclusion Criteria: * Females who are pregnant, nursing, or planning to be pregnant within a year after using this product (or males whose spouse planning to be pregnant); * Subject positive in each of the tests containing treponema pallidum antibody (TP-Ab), human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody at screening. But except the followings: 1. Hepatitis B virus carriers (only HBsAg positive without any hepatitis symptom or sign, and all liver function tests present normal results or abnormal markers without clinical significance by the assessment of investigators); 2. Cured hepatitis C patients (negative in HCV ribonucleic acid (RNA) test); * Subject with assessed survival time of \< 1 year by investigators at screening; * Subject with malignant tumors or a history of malignant tumors at screening; * Subject with infections in lung or other sites, requiring intravenous drug treatment within a week prior to screening; * Subject with more than 4 moderate-to-severe AECOPD, resulting in hospitalization within a year prior to screening; * Subject with one or more pathogenetic or serologic findings of the novel coronavirus infection, or symptoms of suspected infection within 6 weeks prior to screening; * Subject with a history of invasive or noninvasive mechanical ventilation within 4 weeks prior to screening; * Subject who has taken prednisone tablets orally at a dose of ≥ 20 mg/day (or equivalent amount of other oral corticosteroids) within 4 weeks prior to screening; * Subject with major lung diseases other than COPD by assessment of investigators at screening; * Subject with severe systemic diseases other than lung within 6 months prior to screening and assessed to be inappropriate to participate in this trial by investigators; * Subject with severe anemia or poorly controlled granulocyte deficiency, thrombocytopenia by assessment of investigators; * Subject with abnormal coagulation and assessed to be negative for the safety of fiberoptic bronchoscopy operations at screening; * Subject requiring long-term anticoagulation therapy of using antiplatelet coagulant therapeutic agents and disable to discontinue their medications 1 week prior to cell collection and cell infusion as assessed by investigators; * Subject with a risk of suicide, a history of mental illness or a history of epilepsy at screening; * Subject with severe arrhythmias or heart conduction disorders (degree II or above) in 12-lead ECG test at screening; * Subject participated in other clinical trials with interventions within 3 months prior to screening; * Investigators, co-investigators, research coordinators, employees of research participants or research centers, or their family members; * Any circumstance considered to probably increase the risk of patients or interfere with the clinical trial.

Locations (8)

China-Japan Friendship Hospital

Beijing, Beijing Municipality, China

The Southwest Hospital of AMU

Chongqing, Chongqing Municipality, China

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Xiangya Hospital of Central South University

Changsha, Hunan, China

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Shanghai East Hospital

Shanghai, Shanghai Municipality, China

Zhongshan Hospital affiliated to Fudan University

Shanghai, Shanghai Municipality, China

Outcomes

Primary Outcomes

Change of lung diffusing capacity for carbon monoxide (DLCO) from baseline

DLCO is considered a measure of the conductance of CO across the alveolar-capillary membrane and its binding with hemoglobin.

Time frame: Within 52 weeks after treatment

Secondary Outcomes

Change of the alveolar volume (VA) from baseline

Alveolar ventilation is the exchange of gas between the alveoli and the external environment. It is the process by which oxygen is brought into the lungs from the atmosphere and by which the carbon dioxide carried into the lungs in the mixed venous blood is expelled from the body.

Time frame: Winthin 52 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.

Time frame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Change of forced vital capacity (FVC) from baseline

FVC is the full amount of air that can be exhaled with effort in a complete breath.

Time frame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Change of forced expiratory volume in one second (FEV1) from baseline

FEV1 is the volume of breath exhaled with effort in one second.

Time frame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Change of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) from baseline

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.

Time frame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Change of the 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) is also considered when evaluating diffusion function to exclude the effect of lung volume on diffusion volume.

Time frame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 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.

Time frame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Change of modified medical research council (mMRC) dyspnea scale from baseline

It is a questionnaire to evaluate how breathlessness impacts daily activities. According to the degree of activity impacted by shortness of breath, mMRC results are divided into 0-4 grades. Grade 0 means no breathlessness except on strenuous exercise; grade 1 means shortness of breath when hurrying on the level or walking up a slight hill; grade 2 means walking slower than people of same age on the level because of breathlessness or having to stop to catch breath when walking at their own pace on the level; grade 3 means stoping for breath after walking ∼100 m or after few minutes on the level ground; and grade 4 means too breathless to leave the house, or breathless when dressing or undressing.

Time frame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Change of chronic obstructive pulmonary disease Assessment Test (CAT) from baseline

The 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.

Time frame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Annual frequency of exacerbations

Frequency of exacerbations all through the year. A lower frequency means improvement of disease.

Time frame: 1 year after treatment

Symptoms, physical examination

Number of cases with abnormal physical examination findings.

Time frame: Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

12-lead ECG

Number of cases with abnormal 12-lead Electrocardiogram (ECG).

Time frame: 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Blood routine

Number of cases with abnormal laboratory test results.

Time frame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Urine routine

Number of cases with abnormal laboratory test results.

Time frame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Blood biochemistry

Number of cases with abnormal laboratory test results.

Time frame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Function of blood clotting

Number of cases with abnormal function of blood clotting.

Time frame: Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Carcinoembryonic antigen (CEA)

CEA is a tumor marker used for early diagnosis of lung cancer.

Time frame: Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Neuron-specific enolase (NSE)

NSE is a tumor marker significantly elevated in small cell lung cancer.

Time frame: Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment

Cytokeratin-19-fragment (CYFRA21-1)

CYFRA21-1 is a tumor marker which is valuable for the pathological classification and prognosis evaluation of lung cancer.

Time frame: Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 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.

Time frame: Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment