Cystic Fibrosis
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGBMD003 (CFTR mRNA)
Nebulized inhalation of BMD003 (CFTR mRNA) lyophilized preparation. The drug is reconstituted with sterile water for injection to the required concentration before use. Participants receive weekly administration for 12 consecutive weeks. Prior to each administration, airway clearance therapy (e.g., active cycle of breathing technique) is performed as standard care, with short-acting bronchodilators permitted if clinically indicated.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged 12 years and above (inclusive), regardless of gender. 2. Voluntarily sign the informed consent form (legal guardians sign for minors \<18 years old, with minor assent if needed). 3. Confirmed diagnosis of cystic fibrosis (CF) with clinically stable condition. 4. Weight ≥40 kg (≥18 years old) or ≥30 kg (\<18 years old), or deemed eligible by the investigator. 5. Predicted FEV1 ≥40% of the normal value and resting SpO2 ≥92% at screening. 6. SAD trial participants: ≥3 months after last dose, no residual CFTR protein/mRNA in nasal epithelial cells (confirmed by lab tests). 7. Quit smoking for at least 2 years. 8. Willing and able to comply with all study procedures and follow-up plans.
Exclusion criteria
1. Acute respiratory/pulmonary events, significant hemoptysis, or changed CF respiratory medications within 1 month before the first dose. 2. Infected with highly virulent bacteria (e.g., \*Burkholderia cepacia\*, \*Mycobacterium abscessus\*), except for controllable colonization without clinical symptoms. 3. Clinically significant ECG abnormalities (e.g., prolonged QTcF: male \>450ms, female \>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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AE) and serious adverse events (SAE) assessed by CTCAE 6.0 | From first dose up to approximately 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in percent predicted forced expiratory volume in 1 second (ppFEV1) measured by spirometry | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12 | 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 | Baseline, Week 2, Week 4, Week 8, Week 12 | The CFQ-R will be completed by participants at baseline and follow-up visits. The change in total score from baseline will be evaluated. |
Outcome results
None listed