Clinical trial NCT03655808: Autologous Transplantation of Bronchial Basal Cells for Treatment of Bronchiectasis
Official title: Autologous Transplantation of Bronchial Basal Cells for Treatment of Bronchiectasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Bronchiectasis
Keywords: Bronchiectasis
Bronchial basal cells
Autologous transplantation
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Regend Therapeutics
First posted: 2018-08-31
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Diffusing capacity of the lung for carbon monoxide (DLCO)
timeFrame: Week 4, 12, and 24 after treatment
Secondary outcomes:
measure: Forced expiratory volume measured at the first second (FEV1)
timeFrame: Week 4, 12, and 24 after treatment
measure: Forced vital capacity (FVC)
timeFrame: Week 4, 12, and 24 after treatment
measure: The ratio of forced expiratory volume in the first one second to the forced vital capacity (FEV1/FVC)
timeFrame: Week 4, 12, and 24 after treatment
measure: Maximum Mid Expiratory Flow (MMEF)
timeFrame: Week 4, 12, and 24 after treatment
measure: Maximum Voluntary Ventilation (MVV)
timeFrame: Week 4, 12, and 24 after treatment
measure: 6 minute walk distance (6MWD) and distance saturation product (DSP)
timeFrame: Week 4, 12, and 24 after treatment
measure: St. George's Respiratory Questionnaire (SGRQ)
timeFrame: Week 4, 12, and 24 after treatment
measure: FACED scoring
timeFrame: Week 4, 12, and 24 after treatment
measure: Bronchiectasis Severity Index (BSI)
timeFrame: Week 4, 12, and 24 after treatment
measure: High resolution computed tomography (HR-CT) imaging of lung
timeFrame: Week 4, 12, and 24 after treatment
measure: Safety outcomes: adverse events
timeFrame: Through study completion, an average of 24 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai JiaoTong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Yun Feng, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.