Clinical trial NCT05638776: Treatment of Chronic Obstructive Pulmonary Disease (COPD) with Diffusion Capacity Defect by REGEND001 Cell Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Regend Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: The First Affiliated Hospital of Guangzhou Medical University
name: Southwest Hospital, China
name: Shanghai Zhongshan Hospital
name: China-Japan Friendship Hospital
name: Shanghai East Hospital
name: Regend Therapeutics XLotus (Jiangxi) Co, Ltd.
name: The First Affiliated Hospital of Nanchang University
name: Xiangya Hospital of Central South University
name: The First Affiliated Hospital of Soochow University
First posted: 2022-12-06
Enrollment: 58
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Responsive rate (RR) - Ratio of subjects responsive to the treatment
timeFrame: 12 weeks after treatment, 24 weeks after treatment
Secondary outcomes:
measure: Change of lung diffusing capacity for carbon monoxide (DLCO) from baseline
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Change of images of lung by high resolution computed tomography (HR-CT) from baseline
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Change of forced vital capacity (FVC) from baseline
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Change of forced expiratory volume in one second (FEV1) from baseline
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Change of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) from baseline
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Change of the diffusing capacity for carbon monoxide/ the alveolar volume (DLCO/VA) from baseline
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Change of 6-minute-walk test (6MWT) from baseline
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Change of St. George's respiratory questionnaire (SGRQ) scale from baseline
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Change of modified medical research council (mMRC) dyspnea scale from baseline
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Change of chronic obstructive pulmonary disease Assessment Test (CAT) from baseline
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Annual frequency of exacerbations
timeFrame: 1 year after treatment
measure: Body temperature
timeFrame: Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Breathing
timeFrame: Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Pulse
timeFrame: Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Blood pressure
timeFrame: Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Symptoms, physical examination
timeFrame: Baseline, treatment day (D1), 24 hours after treatment, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: 12-lead ECG
timeFrame: 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Blood routine
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Urine routine
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Blood biochemistry
timeFrame: Baseline, 4 weeks after treatment, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Function of blood clotting
timeFrame: Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Carcinoembryonic antigen (CEA)
timeFrame: Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Neuron-specific enolase (NSE)
timeFrame: Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Cytokeratin-19-fragment (CYFRA21-1)
timeFrame: Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
measure: Squamous cell carcinoma antigen (SCC)
timeFrame: Baseline, 12 weeks after treatment, 24 weeks after treatment, 52 weeks after treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
city: Chongqing
country: China
facility: The Southwest Hospital of AMU
state: Chongqing
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital affiliated to Fudan University
state: Shanghai
Study officials:
References: