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

Phase 2

Active, not recruiting

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: REGEND001 cell therapy; Drug: Placebo

• Registration Number: NCT05638776
• Lead Sponsor: Regend Therapeutics

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-06-20
• Study First Submitted: 2022-11-02
• Study First Submitted QC: 2022-11-25
• Study First Posted: 2022-12-06
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-01
• Last Update Posted: 2025-01-03
• Primary Completion: 2025-06
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 58

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
REGEND001 cell therapy	REGEND001 cell therapy	REGEND001 cell therapy
Placebo	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
Responsive rate (RR) - Ratio of subjects responsive to the treatment	12 weeks after treatment, 24 weeks after treatment	Subject is considered to be responsive to the treatment as (1) the DLCO improvement meets MCID at 12 or/and 24 weeks after therapy; and (2) mean of DLCO at 12 and 24 weeks is no less than the baseline value.; MCID of DLCO improvement is 1.1 ml/min/mmHg (0.37 mmol·min -1·kPa-1) for measured value or 11% for a percentage of measured value to predicted value.

Secondary Outcome Measures

Name	Time	Method
Change of lung diffusing capacity for carbon monoxide (DLCO) from baseline	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	DLCO is considered a measure of the conductance of CO across the alveolar-capillary membrane and its binding with hemoglobin. Both measured value and a percentage of measured value to predicted value are evaluated.
Change of images of lung by high resolution computed tomography (HR-CT) from baseline	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	HR-CT images of lung will be analyzed to indicate the change of pulmonary structure.
Change of forced vital capacity (FVC) from baseline	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	FVC is the full amount of air that can be exhaled with effort in a complete breath.
Change of forced expiratory volume in one second (FEV1) from baseline	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	FEV1 is the volume of breath exhaled with effort in one second.
Change of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) from baseline	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	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.
Change of the diffusing capacity for carbon monoxide/ the alveolar volume (DLCO/VA) from baseline	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	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.
Change of 6-minute-walk test (6MWT) from baseline	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	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.
Change of St. George's respiratory questionnaire (SGRQ) scale from baseline	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	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.
Change of modified medical research council (mMRC) dyspnea scale from baseline	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	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.
Change of chronic obstructive pulmonary disease Assessment Test (CAT) from baseline	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	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.
Annual frequency of exacerbations	1 year after treatment	Frequency of exacerbations all through the year. A lower frequency means improvement of disease.
Body temperature	Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	Number of cases with abnormal physical examination findings.
Breathing	Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	Number of cases with abnormal physical examination findings.
Pulse	Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	Number of cases with abnormal physical examination findings.
Blood pressure	Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	Number of cases with abnormal physical examination findings.
Symptoms, physical examination	Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	Number of cases with abnormal physical examination findings.
12-lead ECG	4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	Number of cases with abnormal 12-lead Electrocardiogram (ECG).
Blood routine	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	Number of cases with abnormal laboratory test results.
Urine routine	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	Number of cases with abnormal laboratory test results.
Blood biochemistry	Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	Number of cases with abnormal laboratory test results.
Function of blood clotting	Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	Number of cases with abnormal function of blood clotting.
Carcinoembryonic antigen (CEA)	Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	CEA is a tumor marker used for early diagnosis of lung cancer.
Cytokeratin-19-fragment (CYFRA21-1)	Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	CYFRA21-1 is a tumor marker which is valuable for the pathological classification and prognosis evaluation of lung cancer.
Squamous cell carcinoma antigen (SCC)	Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	SCC is a specific marker for lung squamous cell carcinoma.Tumor markers are monitored to assess the safety.
Neuron-specific enolase (NSE)	Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment	NSE is a tumor marker significantly elevated in small cell lung cancer.

Trial Locations

Locations (8)

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

China-Japan Friendship Hospital; 🇨🇳 Beijing, Beijing, China

The Southwest Hospital of AMU; 🇨🇳 Chongqing, Chongqing, China

The First Affiliated Hospital of Guangzhou Medical University; 🇨🇳 Guangzhou, Guangdong, China

Shanghai East Hospital; 🇨🇳 Shanghai, Shanghai, China

Zhongshan Hospital affiliated to Fudan University; 🇨🇳 Shanghai, Shanghai, China