Autologous Transplantation of Bronchial Basal Cells for Treatment of Bronchiectasis

NCT03655808 | Completed Phase 1

• 1 other identifier: 201810
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Bronchiectasis is a disease resulted from progressive destruction of bronchi with no effective drug for its treatment. In this study, we intends to carry out a randomized, single-blinded, controlled pilot clinical trial at 1/2 phase. During the process, autologous bronchial basal cells (BBCs) will be dissected from trial tissue via 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 airway clearance. The investigators will evaluate the safety and effectiveness of the treatment by measuring a serial of indicators, including occurrence of adverse events, pulmonary function, 6 minute walk distance (6MWD), the distance-saturation product (DSP), St. George's Respiratory Questionnaire (SGRQ), FACED scoring, bronchiectasis severity index (BSI) , and high-resolution computed tomography (HRCT) at week 4, week 12, and week 24 after cell transplantation.

Conditions

Bronchiectasis

Keywords

Bronchiectasis; Bronchial basal cells; Autologous transplantation

Outcome Measures

Primary Outcomes (1)

• Diffusing capacity of the lung for carbon monoxide (DLCO)

  An indicator of pulmonary function

  Week 4, 12, and 24 after treatment

Secondary Outcomes (11)

• Forced expiratory volume measured at the first second (FEV1)

  Week 4, 12, and 24 after treatment

• Forced vital capacity (FVC)

  Week 4, 12, and 24 after treatment

• The ratio of forced expiratory volume in the first one second to the forced vital capacity (FEV1/FVC)

  Week 4, 12, and 24 after treatment

• Maximum Mid Expiratory Flow (MMEF)

  Week 4, 12, and 24 after treatment

• Maximum Voluntary Ventilation (MVV)

  Week 4, 12, and 24 after treatment

Study Arms (2)

Cell treatment group

EXPERIMENTAL

Patients receive both autologous BBCs transplantation and B-ACT therapy.

Biological: Bronchial basal cells (BBCs); Procedure: Bronchoscopic airway clearance treatment （B-ACT）

Control group

SHAM COMPARATOR

Patients only receive B-ACT therapy.

Procedure: Bronchoscopic airway clearance treatment （B-ACT）

Interventions

Bronchial basal cells (BBCs) BIOLOGICAL

Airway epithelial cells were collected in patients of the cell treatment group by a disposable 2-mm brush in order to obtain BBCs. The obtained tissue were washed and enzymatically digested to form a single-cell suspension, which was then cultured under R-Clone system, a patented technique of Regend Therapeutics, Ltd.. For patients in the cell treatment group, on the basis of B-ACT therapy, they were also received autologous BBCs transplantation. Cell suspension was diluted with normal saline. Fibrotic bronchoscopy was guided into the lobular or segmental airways and cells were instilled into lobes.

Also known as: P63+ lung stem/progenitor cells, Airway basal cells, Lung stem/progenitor cells

Cell treatment group

Bronchoscopic airway clearance treatment （B-ACT） PROCEDURE

The bronchoscopy was performed by board-certified respiratory physicians of Ruijin Hospital using a flexible fiber-optic bronchoscope. B-ACT therapy was performed on all patients in both groups according to the protocol. In brief, continuous suction was performed with the sputum aspirator from the trachea to the subsegmental during the entering of bronchoscope to remove the visible secretions from entire respiratory tract, and then operators used normal saline to collect lavage fluid (the volume various depending on the operator's judgement).

Cell treatment group; Control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects diagnosed as bronchiectasis.
• Subjects with a DLCO \< 80% predicted value.
• Subjects with stable condition for more than 2 weeks.
• Subjects can do pulmonary function tests.
• Subjects can tolerate bronchoscopy.
• Subjects signed informed consent.

You may not qualify if:

• Women of childbearing age at the stage of pregnancy or lactation, or those without taking effective contraceptive measures.
• Subjects with positive serological tests for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or syphilis (HBV carriers and patients with stable chronic hepatitis B could be accepted if titers of HBV DNA \< 500 IU/mL or copies \< 1000 copies/mL; patients with curative hepatitis C were eligible if HCV RNA tests were negative).
• Subjects with any malignancy.
• Subjects with any of the following pulmonary diseases: active tuberculosis, pulmonary embolism, pneumothorax, multiple huge bullae, uncontrolled asthma, acute exacerbation of chronic bronchitis or extremely severe COPD.
• Subjects with other serious diseases, such as poorly controlled 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.

Sponsors & Collaborators

• Ruijin Hospital: lead
• Regend Therapeutics: collaborator

Study Sites (1)

Ruijin Hospital Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

Related Publications (3)

• 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.

  PMID: 25383540 BACKGROUND

• 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.

  PMID: 29344809 BACKGROUND

• Yan J, Zhang W, Feng Y, Liu X, Niu L, Guo Y, Zhou L, Shi M, Di C, Zhang Q, Wang X, Zhou J, Dai R, Ni L, Bao Z, Yan T, Hu Y, Wang P, Zhang T, Zhou M, Zuo W, Qu J. Autologous transplantation of P63+ lung progenitor cells in patients with bronchiectasis: A randomized, single-blind, controlled trial. Cell Rep Med. 2024 Nov 19;5(11):101819. doi: 10.1016/j.xcrm.2024.101819.

  PMID: 39566467 DERIVED

MeSH Terms

Conditions

Bronchiectasis

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Study Officials

• Yun Feng, M.D., Ph.D

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The opaque sealed envelope method was used to conceal the allocation sequence. Both patients and investigators, except for the bronchoscopy operators, remained masked to the treatment assignment for the duration of the study. Only the investigators who performed the bronchoscopy were unblinded. The non-blinded investigators should not disclose any blind information to other investigators, participants, care providers, or outcomes assessors.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Eligibility patients were randomly assigned in a 1:1 ratio to receive either autologous cell transplantation therapy (cell treatment group) or bronchoscopic airway clearance treatment (B-ACT therapy, control group).

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: August 31, 2018
• Study Start: June 21, 2020
• Primary Completion: May 17, 2023
• Study Completion: May 17, 2023
• Last Updated: December 5, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)