Safety and Efficacy of Nebulized 3D-cultured Human Placental Mesenchymal Stem Cell-derived Extracellular Vesicles (hPMSC-EVs) for Idiopathic Pulmonary Fibrosis

A Single-center, Open-label, Single and Multiple Dose, Dose-escalation Exploratory 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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Idiopathic Pulmonary Fibrosis (IPF)
• Intervention / Treatment: Biological: 3D-cultured human placental mesenchymal stem cell-derived extracellular vesicles; Biological: 3D-cultured human placental mesenchymal stem cell-derived extracellular vesicles; Biological: 3D-cultured human placental mesenchymal stem cell-derived extracellular vesicles

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Huan Ye, MD; Phone Number: 010-89509000; Email: ye.huan@bjchest.org.cn

Study Locations

• China
  • Beijing, China
    • Beijing chest hospital, Capital Medical University
    • Contact: Huan Ye, MD; Phone Number: 010-89509000; Email: yedahuan@yeah.net
    • Principal Investigator: Huan Ye, MD
    • Principal Investigator: Jingtao Gao, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1; Level 1: 1.0×10⁹ particles per treatment	Biological: 3D-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.; Other Names: hPMSC-EVs; Biological: 3D-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: 2.0×10⁹particles per treatment, administered twice daily (9:00±30 min and 20:00±30 min) for 7 consecutive days per treatment course.; Other Names: hPMSC-EVs; Biological: 3D-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: 3.0×10⁹ particles per treatment, administered twice daily (9:00±30 min and 20:00±30 min) for 7 consecutive days per treatment course.; Other Names: hPMSC-EVs
Experimental: Dose Level 2; Level 2: 2.0×10⁹ particles per treatment	Biological: 3D-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.; Other Names: hPMSC-EVs; Biological: 3D-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: 2.0×10⁹particles per treatment, administered twice daily (9:00±30 min and 20:00±30 min) for 7 consecutive days per treatment course.; Other Names: hPMSC-EVs; Biological: 3D-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: 3.0×10⁹ particles per treatment, administered twice daily (9:00±30 min and 20:00±30 min) for 7 consecutive days per treatment course.; Other Names: hPMSC-EVs
Experimental: Dose Level 3; 3.0×10⁹ particles per treatment	Biological: 3D-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.; Other Names: hPMSC-EVs; Biological: 3D-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: 2.0×10⁹particles per treatment, administered twice daily (9:00±30 min and 20:00±30 min) for 7 consecutive days per treatment course.; Other Names: hPMSC-EVs; Biological: 3D-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: 3.0×10⁹ particles per treatment, administered twice daily (9:00±30 min and 20:00±30 min) for 7 consecutive days per treatment course.; Other Names: hPMSC-EVs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)	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.	From first dose to 4 weeks after last dose (up to Day 35)
Maximum tolerated dose (MTD) of nebulized hPMSC-EVs	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.	During the first 7-day treatment course and follow-up to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in forced vital capacity (FVC % predicted) from baseline	Absolute and percent change in predicted forced vital capacity (FVC) from baseline to Day 8, Day 28, and Day 84.	Baseline, Day 8, Day 28, Day 84
Change in diffusing capacity of the lung for carbon monoxide (DLCO % predicted) from baseline	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.	Baseline, Day 8, Day 28, Day 84
Change in 6-minute walking distance (6MWD) from baseline	Absolute and percent change in 6-minute walking distance (6MWD) from baseline to Day 8, Day 28, and Day 84.	Baseline, Day 8, Day 28, Day 84
Change in Saint George's Respiratory Questionnaire (SGRQ) total score from baseline	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.	Baseline, Day 8, Day 28, Day 84
Change in chest high-resolution computed tomography (HRCT) findings from baseline	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.	Baseline, Day 28, Day 84

Collaborators and Investigators

• Sponsor: Huan Ye
• Investigators: Principal Investigator: Jingtao Gao, MD, Beijing chest hospital, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Mesenchymal Stem Cells; Idiopathic Pulmonary Fibrosis; Stem Cell Therapy; Extracellular Vesicles
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: KY-2026-1 (Other Identifier: Beijing Chest Hospital, Capital Medical University)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No