Autologous Transplantation of Bronchial Basal Cells for Treatment of COPD

Autologous Transplantation of Bronchial Basal Cells for Treatment of Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by long-term poor airflow, resulting in chronic pulmonary heart disease, chronic respiratory failure or even death. Till now, the damaged pulmonary bronchus structures in COPD patients cannot be repaired by recent clinical methods so far. In this study, we intends to carry out a single-centered, non-randomized and self-controlled clinical trial at an early phase. During the process, autologous bronchial basal cells (BBCs) will be dissected from trial tissue from bronchoscopic brushing. Then the BBCs will be expanded and detected by quality control. In the following, qualified BBCs will be injected directly into the lesion by fiberoptic bronchoscopy after lavage. After six-month observation, the investigators will evaluate the safety and effectiveness of the treatment by measuring a serial of indicators, including occurrence of adverse events, pulmonary function, the CT imaging, 6 minute walk distance (6MWD), St. George's Respiratory Questionnaire (SGRQ), modified medical research council (mMRC) dyspnea scale and COPD assessment test (CAT).

Study Overview

• Status: Unknown
• Conditions: COPD
• Intervention / Treatment: Biological: Bronchial basal cells

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wei Zuo, Ph. D; Phone Number: +86-21-65985082; Email: zuow@regend.cn
• Study Contact Backup: Name: Jieming Qu, M.D., Ph.D; Phone Number: +86-21-64370045; Email: jmqu0906@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects aged between 40 to 75.
• Subjects diagnosed with COPD and meet the following standards: a.sustained airway obstruction; b.presence of persistent airflow limitation confirmed by post-bronchodilator FEV1<70% predicted value and FEV1/FVC < 0.7.
• Subjects with pulmonary emphysema confirmed by imaging evidence.
• Subjects with DLCO<80% predicted value in pulmonary function test.
• Subjects with stable condition for more than 4 weeks.
• Subjects tolerant to bronchoscopy.
• Subjects signed informed consent.

Exclusion Criteria:

• Pregnant or lactating women.
• Subjects with syphilis or any of HIV, HBV, HCV positive antibody.
• Subjects with any malignancy.
• Subjects suffering from any of the following pulmonary diseases: asthma, active tuberculosis, pulmonary embolism, pneumothorax, pulmonary artery hypertension or interstitial lung disease.
• Subjects suffering from other serious diseases, such as diabetes, myocardial infarction, unstable angina, cirrhosis, and acute glomerulonephritis.
• Subjects with leukopenia (WBC less than 4x10^9 / L) or agranulocytosis (WBC less than 1.5x10^9 / L or neutrophils less than 0.5x10^9 / L) caused by any reason.
• Subjects with severe renal impairment, serum creatinine> 1.5 times of the upper limit of normal.
• Subjects with liver disease or liver damage: ALT, AST, total bilirubin> 2 times of the upper limit of normal.
• Subjects with a history of mental illness or suicide risk, with a history of epilepsy or other central nervous system disorders.
• Subjects with severe arrhythmias (such as ventricular tachycardia, frequent superventricular tachycardia, atrial fibrillation, and atrial flutter, etc.) or cardiac degree II or above conduction abnormalities displayed via 12-lead ECG.
• Subjects with a history of alcohol or illicit drug abuse.
• Subjects accepted by any other clinical trials within 3 months before the enrollment.
• Subjects with poor compliance, difficult to complete the study.
• Any other conditions that might increase the risk of subjects or interfere with the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bronchial basal cells; Autologous transplantation of bronchial basal cells	Biological: Bronchial basal cells; Autologous transplantation of bronchial basal cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diffusing capacity of the lung for carbon monoxide (DLCO)	An indicator for pulmonary function	6 months -1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced expiratory volume measured at the first second (FEV1)	One of the indicators in pulmonary function test, a marker to assess airway obstruction	6 months -1 year
Forced vital capacity (FVC)	One of the indicators in pulmonary function test, indicating the maximum amount of air a person can expel from the lungs after a maximum inhalation	6 months -1 year
The ratio of forced expiratory volume in the first one second to the forced vital capacity (FEV1/FVC)	One of the indicators in pulmonary function test, representing the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration to the full vital capacity	6 months -1 year
Maximum Mid Expiratory Flow (MMF)	One of the indicators in pulmonary function test, standing for maximal (mid-)expiratory flow and is the peak of expiratory flow as taken from the flow-volume curve and measured in liters per second	6 months -1 year
Maximum Voluntary Ventilation (MVV)	One of the indicators in pulmonary function test, measuring the maximum amount of air that can be inhaled and exhaled within one minute	6 months -1 year
6-minute-walk test (6MWT)	An indicator to evaluate the exercise function of patients with moderate or severe pulmonary heart diseases	6 months -1 year
Imaging of lung structure by high resolution computed tomography (HR-CT)	Images of lung will be analyzed to indicate the newly-derived pulmonary structure.	6 months -1 year
Assess life quality affected by the respiratory problem by St. George's respiratory questionnaire (SGRQ) scale	Total scores (0-100) will be calculated and compared before and after transplantation, and higher values represent a better outcome.	6 months -1 year
Modified medical research council (mMRC) chronic dyspnea scale to evaluate the level of dyspnea	mMRC Dyspnea Scale scores (1-5) will be measured and compared before and after transplantation, and lower values represent a better outcome.	6 months -1 year
COPD Assessment Test (CAT)	A patient-completed questionnaire assessing all aspects of the impact of COPD	6 months -1 year

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Collaborators: Regend Therapeutics
• Investigators: Principal Investigator: Yun Feng, M.D., Ph.D, Ruijin Hospital

Publications and helpful links

General Publications

• Zuo W, Zhang T, Wu DZ, Guan SP, Liew AA, Yamamoto Y, Wang X, Lim SJ, Vincent M, Lessard M, Crum CP, Xian W, McKeon F. p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration. Nature. 2015 Jan 29;517(7536):616-20. doi: 10.1038/nature13903. Epub 2014 Nov 12.
• Ma Q, Ma Y, Dai X, Ren T, Fu Y, Liu W, Han Y, Wu Y, Cheng Y, Zhang T, Zuo W. Regeneration of functional alveoli by adult human SOX9+ airway basal cell transplantation. Protein Cell. 2018 Mar;9(3):267-282. doi: 10.1007/s13238-018-0506-y. Epub 2018 Jan 17.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2018
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): March 1, 2021

Study Registration Dates

• First Submitted: August 22, 2018
• First Submitted That Met QC Criteria: August 30, 2018
• First Posted (Actual): August 31, 2018

Study Record Updates

• Last Update Posted (Actual): November 6, 2018
• Last Update Submitted That Met QC Criteria: November 4, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 201809

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No