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

This is a prospective, single-center, open-label, multiple-dose clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of inhaled BMD003 (CFTR mRNA) administered repeatedly in Chinese patients with cystic fibrosis aged 12 years and older.

BMD003 is an investigational nebulized mRNA therapy that expresses functional human CFTR protein in airway epithelial cells to address the underlying genetic defect of cystic fibrosis. Eligible patients will receive once-weekly inhaled BMD003 for 12 consecutive weeks, followed by a long-term follow-up period to monitor safety, durability of effect, and clinical outcomes.

The primary objective is to evaluate the safety and tolerability of repeated inhaled BMD003 by assessing adverse events (AEs), serious adverse events (SAEs), clinical laboratory tests, vital signs, physical examinations, 12-lead ECG, pulmonary function, and other safety parameters throughout the study.

The secondary objective is to assess preliminary efficacy by measuring changes from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) and in the score of the Cystic Fibrosis Questionnaire-Revised (CFQ-R).

Exploratory objectives include characterization of pharmacokinetic (PK) profiles in blood and sputum, evaluation of immunogenicity, assessment of sputum properties, sweat chloride concentration, nasal epithelial cell biomarkers, daily sputum volume, and other exploratory endpoints related to disease status and treatment response.

Inclusion criteria

• 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.
• Predicted FEV1 ≥40% of the normal value and resting SpO2 ≥92% at screening.
• SAD trial participants: ≥3 months after last dose, no residual CFTR protein/mRNA in nasal epithelial cells (confirmed by lab tests).
• Quit smoking for at least 2 years.
• Willing and able to comply with all study procedures and follow-up plans.

Exclusion criteria

• 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).
• History of solid organ/bone marrow transplantation or on transplant waiting list.
• Positive HIV, syphilis, HBsAg or HCV antibodies at screening.
• Participated in inhaled drug/device studies or used CFTR modulators within 30 days before screening.
• Pregnant or lactating females.
• A history of allergies to inhaled drug components or other allergies deemed contraindicated by the investigator.
• Any other medical conditions/circumstances that may interfere with the trial (judged by the investigator)