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
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Dose Level 1
Level 1: 1.0×10⁹ particles per treatment
干预措施: 3D-cultured human placental mesenchymal stem cell-derived extracellular vesicles (Biological)
Dose Level 2
Level 2: 2.0×10⁹ particles per treatment
干预措施: 3D-cultured human placental mesenchymal stem cell-derived extracellular vesicles (Biological)
Dose Level 3
3.0×10⁹ particles per treatment
干预措施: 3D-cultured human placental mesenchymal stem cell-derived extracellular vesicles (Biological)
结局指标
主要结局
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 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
时间窗: 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.
次要结局
- Change in forced vital capacity (FVC % predicted) from baseline(Baseline, Day 8, Day 28, Day 84)
- Change in diffusing capacity of the lung for carbon monoxide (DLCO % predicted) from baseline(Baseline, Day 8, Day 28, Day 84)
- Change in 6-minute walking distance (6MWD) from baseline(Baseline, Day 8, Day 28, Day 84)
- Change in Saint George's Respiratory Questionnaire (SGRQ) total score from baseline(Baseline, Day 8, Day 28, Day 84)
- Change in chest high-resolution computed tomography (HRCT) findings from baseline(Baseline, Day 28, Day 84)
研究者
Huan Ye
Chief Physician, Professor
Beijing Chest Hospital