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.
Aged 12 years and above (inclusive), regardless of gender.
Voluntarily sign the informed consent form (legal guardians sign for minors <18 years old, with minor assent if needed).
Confirmed diagnosis of cystic fibrosis (CF) with clinically stable condition.
Weight ≥40 kg (≥18 years old) or ≥30 kg (<18 years old), or deemed eligible by the investigator.
Acute respiratory/pulmonary events, significant hemoptysis, or changed CF respiratory medications within 1 month before the first dose.
Infected with highly virulent bacteria (e.g., *Burkholderia cepacia*, *Mycobacterium abscessus*), except for controllable colonization without clinical symptoms.
Clinically significant ECG abnormalities (e.g., prolonged QTcF: male >450ms, female >460ms) at screening.
Abnormal liver/kidney function at screening (TBIL >ULN, ALT/AST >3×ULN, CRE ≥1.5×ULN).
Single group
BMD003 (CFTR mRNA)
DrugNebulized inhalation of BMD003 (CFTR mRNA) lyophilized preparation. The drug is reconstituted with sterile water for injection to the required concentration before use.
Incidence of adverse events (AE) and serious adverse events (SAE) assessed by CTCAE 6.0
All adverse events (AEs) and serious adverse events (SAEs) will be monitored and recorded throughout the study. Severity will be graded using the NCI CTCAE version 6.0, and their relationship to the study drug will be evaluated at each study visit.
Change in percent predicted forced expiratory volume in 1 second (ppFEV1) measured by spirometry
ppFEV1 will be measured by standardized spirometry at baseline and scheduled visits. The change from baseline will be calculated and analyzed.
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) score
The CFQ-R will be completed by participants at baseline and follow-up visits. The change in total score from baseline will be evaluated.
Change in sweat chloride concentration measured by quantitative pilocarpine iontophoresis
Sweat chloride concentration will be measured at baseline and scheduled visits. The change from baseline will be evaluated.
Change in daily sputum production volume
Daily sputum production will be collected and weighed by participants. The change from baseline will be assessed.
Change in sputum solid content
Sputum solid content will be measured at baseline and scheduled visits. The change from baseline will be analyzed.
Incidence of treatment-related adverse events (TRAE) graded by CTCAE 6.0
Treatment-related adverse events will be monitored and graded using NCI CTCAE version 6.0 throughout the study.
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