Idiopathic Pulmonary Fibrosis (IPF)
Conditions
Keywords
Idiopathic Pulmonary Fibrosis, Extracellular Vesicles, Mesenchymal Stem Cells, Stem Cell Therapy
Brief summary
This is a single-center, open-label, dose-escalation clinical study to evaluate the safety and efficacy of nebulized 3D-cultured human placental mesenchymal stem cell-derived extracellular vesicles (hPMSC-EVs) in patients with idiopathic pulmonary fibrosis (IPF). Eligible participants will be assigned to one of three dose groups (1.0×10⁹, 2.0×10⁹, or 3.0×10⁹ particles per treatment) using a 3+3 design. All participants will receive nebulized hPMSC-EVs twice daily for 7 consecutive days. The main purpose of this study is to assess the safety and tolerability of hPMSC-EVs, including the incidence of adverse events, changes in vital signs, laboratory tests, and immune markers. Secondary objectives include evaluating changes in lung function (FVC, DLCO), 6-minute walking distance, respiratory symptoms (SGRQ score), and chest HRCT findings. Participants will undergo screening visits, treatment administration, and follow-up visits up to 12 months after the first dose to monitor safety and efficacy outcomes.
Interventions
BIOLOGICAL3D-cultured human placental mesenchymal stem cell-derived extracellular vesicles
3D-cultured human placental mesenchymal stem cell-derived extracellular vesicles (hPMSC-EVs) are administered via nebulization inhalation. The intervention is diluted in 6 mL of normal saline to a total volume of 7.5 mL, and delivered using a vibrating mesh nebulizer to target the lower respiratory tract. Three dose levels are evaluated: 1.0×10⁹ particles per treatment, administered twice daily (9:00±30 min and 20:00±30 min) for 7 consecutive days per treatment course.
Sponsors
Huan Ye
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 75 years, male or female at the time of signing the informed consent form. * Confirmed diagnosis of idiopathic pulmonary fibrosis (IPF) in accordance with the 2022 ATS/ERS/JRS/ALAT clinical criteria. * Forced vital capacity (FVC) ≥50% and ≤80% of predicted value, and hemoglobin-corrected diffusing capacity of the lung for carbon monoxide (DLCO) ≥30% and ≤80% of predicted value at screening. * Stable dose of antifibrotic therapy (nintedanib, pirfenidone, or nerandomilast) for at least 8 weeks prior to screening. * 6-minute walking distance (6MWD) \>150 meters at screening. * Willing to use effective contraception during the study and for 12 months after the last dose of study treatment (for subjects of childbearing potential, including male subjects whose spouses are of childbearing potential). * Signed and dated written informed consent form prior to any study-related procedures. * Able to comply with all study procedures and scheduled follow-up visits.
Exclusion criteria
* Prior treatment with stem cell-derived products or extracellular vesicles for any disease. * Inability to tolerate nebulized inhalation therapy. * History of severe drug allergy or anaphylaxis to any component of the study treatment or nebulization materials. * Diagnosis of bronchial asthma or other active respiratory diseases that may interfere with study assessments. * Pregnant, breastfeeding, or planning pregnancy within 12 months after the last dose of study treatment. * Malignancy within 5 years prior to screening (except adequately treated basal cell carcinoma or cervical carcinoma in situ). * Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). * History of solid organ or hematopoietic stem cell transplantation, or being on the transplant waiting list. * Requirement for long-term oxygen therapy for more than 15 hours per day. * Severe cardiac, hepatic, renal, or other systemic diseases that, in the investigator's judgment, would compromise study participation or confound study results. * Participation in another interventional clinical trial within 3 months prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) | From first dose to 4 weeks after last dose (up to Day 35) | Incidence and severity of all adverse events (AEs) and serious adverse events (SAEs) from first dose administration to 4 weeks after the last dose, graded according to NCI-DAIDS criteria. |
| Maximum tolerated dose (MTD) of nebulized hPMSC-EVs | During the first 7-day treatment course and follow-up to Day 28 | Maximum tolerated dose (MTD) defined as the highest dose level with ≤1 dose-limiting toxicity (DLT) observed in 3 participants during the first treatment course. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in forced vital capacity (FVC % predicted) from baseline | Baseline, Day 8, Day 28, Day 84 | Absolute and percent change in predicted forced vital capacity (FVC) from baseline to Day 8, Day 28, and Day 84. |
| Change in diffusing capacity of the lung for carbon monoxide (DLCO % predicted) from baseline | Baseline, Day 8, Day 28, Day 84 | Absolute and percent change in hemoglobin-corrected predicted diffusing capacity of the lung for carbon monoxide (DLCO) from baseline to Day 8, Day 28, and Day 84. |
| Change in 6-minute walking distance (6MWD) from baseline | Baseline, Day 8, Day 28, Day 84 | Absolute and percent change in 6-minute walking distance (6MWD) from baseline to Day 8, Day 28, and Day 84. |
| Change in Saint George's Respiratory Questionnaire (SGRQ) total score from baseline | Baseline, Day 8, Day 28, Day 84 | Change in Saint George's Respiratory Questionnaire (SGRQ) total score and domain scores (Symptoms, Activity, Impact) from baseline to Day 8, Day 28, and Day 84. A lower score indicates better respiratory-related quality of life. |
| Change in chest high-resolution computed tomography (HRCT) findings from baseline | Baseline, Day 28, Day 84 | Change in interstitial lung disease extent and fibrosis score on chest high-resolution computed tomography (HRCT) from baseline to Day 28 and Day 84, evaluated by two independent radiologists. |
Countries
China
Contacts
CONTACTHuan Ye, MD
PRINCIPAL_INVESTIGATORJingtao Gao, MD
Beijing Chest Hospital, Capital Medical University
Outcome results
None listed