Safety and Efficacy of Inhaled BMD003 (CFTR mRNA) in Chinese Cystic Fibrosis Patients Aged ≥12 Years

This is a prospective, single-center, open-label clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of inhaled BMD003 (CFTR mRNA) in Chinese patients aged 12 years and above with cystic fibrosis (CF) following multiple administrations. Additionally, the study aims to explore the pharmacokinetic characteristics, immunogenicity, and relevant biomarkers of the drug. The study adopts a multiple-dose escalation design. Eligible patients will be sequentially enrolled into different cohorts, and the next cohort may receive a higher dose only after the safety data review of the previous dose cohort is completed. The entire study consists of four phases: screening period, safety observation period, continuous treatment period, and long-term follow-up period. Participants will receive nebulized inhalation of the study drug at the specified frequency. During the study, blood, sputum samples, and nasal swabs will be collected at designated time points for pharmacokinetic, immunogenicity, cytokine, and other related detections. Moreover, lung function tests, chest imaging, electrocardiograms, sweat chloride concentration tests, and other examinations will be performed at each visit. Meanwhile, the Cystic Fibrosis Questionnaire-Revised (CFQ-R) will be used to assess the patients' health-related quality of life, so as to comprehensively evaluate the safety and efficacy of the study drug. Adverse events will be closely monitored and recorded throughout the study. The safety of the study drug will be comprehensively evaluated by summarizing various safety indicators such as adverse events and laboratory tests. All statistical analyses will be performed using professional statistical software, and descriptive statistical methods will be employed to analyze the safety, efficacy, pharmacokinetic, and other related data of the study drug. The total duration of this study is 1 year, which is intended to provide a basis for the selection of the recommended dose for Phase Ⅱ clinical trials.

Inclusion Criteria: 1. Aged 12 years and above (inclusive), regardless of gender. 2. Voluntarily sign the informed consent form (legal guardians sign for minors \460ms) at screening. 4. Abnormal liver/kidney function at screening (TBIL \>ULN, ALT/AST \>3×ULN, CRE ≥1.5×ULN). 5. History of solid organ/bone marrow transplantation or on transplant waiting list. 6. Positive HIV, syphilis, HBsAg or HCV antibodies at screening. 7. Participated in inhaled drug/device studies or used CFTR modulators within 30 days before screening. 8. Pregnant or lactating females. 9. A history of allergies to inhaled drug components or other allergies deemed contraindicated by the investigator. 10. Any other medical conditions/circumstances that may interfere with the trial (judged by the investigator)