An Open Clinical Study to Explore the Safety, Tolerance and Preliminary Efficacy of Human Umbilical Cord Mesenchymal Stem Cell Injection in the Treatment of Idiopathic Pulmonary Fibrosis (IPF)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Tolerance of patients with idiopathic fibrosis to human umbilical cord mesenchymal stem cell injection
研究概览
简要总结
Main purpose
-To explore the safety and tolerance of human umbilical cord mesenchymal stem cells in the treatment of idiopathic pulmonary fibrosis (IPF).
Secondary purpose
- To explore the preliminary efficacy of human umbilical cord mesenchymal stem cells in the treatment of idiopathic pulmonary fibrosis (IPF), and to recommend the appropriate dose of cell therapy for subsequent clinical studies.
- To explore the immunogenicity of human umbilical cord mesenchymal stem cell injection in the treatment of idiopathic pulmonary fibrosis (IPF).
This study adopts a clinical research design of multi center, single dose and increasing dose.
18 qualified IPF subjects will be included in this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 40-75 years (inclusive), regardless of gender;
- •Diagnosed with idiopathic pulmonary fibrosis (IPF) according to the 2018 diagnostic guidelines jointly issued by the American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Association (ALAT);
- •Subjects with typical HRCT imaging manifestations of IPF (honeycombing, traction bronchiectasis or bronchiolectasis (mainly appearing in ground-glass opacities and fine reticular opacities)) within 12 months prior to screening;
- •Subjects whose disease is assessed by the investigator as stable within 3 months prior to dosing, with diffusing capacity for carbon monoxide (DLCO) at 30%-79% of the predicted value (adjusted for Hb), and FVC/predicted value ≥50%;
- •Blood biochemical tests must meet the following criteria: alanine aminotransferase (ALT) ≤1.5×ULN, aspartate aminotransferase (AST) ≤1.5×ULN, total bilirubin (TBIL) ≤1.5×ULN, direct bilirubin (DBIL) ≤1.5×ULN, serum creatinine (Cr) ≤1.5×ULN;
- •Expected survival ≥12 months;
- •Subjects with good compliance, who are able to understand and cooperate in performing pulmonary function tests, and are willing to receive medication as required by the protocol and undergo follow-up examinations on schedule;
- •Subjects who voluntarily participate in the trial, understand, and sign the informed consent form.
排除标准
- •Subjects, who have previously received stem cell therapy, are intolerant to cell therapy, or have taken drugs that may cause or exacerbate pulmonary fibrosis (such as amiodarone, bleomycin, or methotrexate, etc.);
- •Subjects with interstitial lung disease (ILD) other than IPF, including but not limited to: any other type of interstitial pneumonia; lung diseases associated with exposure to fibrogenic agents or other environmental toxins or drugs; other types of occupational lung diseases; granulomatous lung diseases; pulmonary vascular diseases; systemic diseases, including vasculitis, infectious diseases (i.e., tuberculosis), and connective tissue diseases;
- •Subjects currently requiring oxygen therapy (oxygen therapy time ≥15 hours/day);
- •Subjects with a history of mechanical ventilation or concurrent infectious pneumonia or asthma within 1 month prior to screening;
- •Subjects with a history of malignancy within 5 years prior to screening;
- •Subjects who have been hospitalized three or more times due to acute exacerbation of IPF or other respiratory diseases within 1 year prior to screening;
- •Evidence of current digestive, urinary, cardiovascular, cerebrovascular, hematological, neurological, psychiatric, or metabolic diseases that may affect safety, such as poorly controlled type 2 diabetes (fasting blood glucose ≥10.0 mmol/L or HbA1c ≥8.5%) or poorly controlled hypertension (≥160/100 mmHg).
- •History of psychotropic drug abuse or drug addiction;
- •Known history of immune system diseases (e.g., thymic diseases, systemic lupus erythematosus);
- •Subjects with positive serological virology tests (HBsAg, HCV antibody, HIV antibody, Treponema pallidum antibody); however, hepatitis B virus carriers, stable hepatitis B patients after drug treatment (DNA titer ≤500 IU/mL or copy number <1000 copies/mL), and cured hepatitis C patients (HCV RNA negative) may be enrolled after being deemed eligible by the investigator;
- •Subjects allergic to human albumin, anesthetic drugs, or any of their components;
- •Subjects who have participated in any other clinical trial within 3 months prior to screening;
- •Subjects who cannot tolerate bronchoscopy (including but not limited to the following conditions: active massive hemoptysis; severe hypertension and arrhythmia; myocardial infarction within 4-6 weeks prior to screening or history of unstable angina; severe cardiopulmonary dysfunction; uncorrectable bleeding tendency (platelet count <60×109/L), such as severe coagulation disorders, uremia, and severe pulmonary hypertension; severe superior vena cava obstruction syndrome; suspected aortic aneurysm; multiple pulmonary bullae; extreme systemic exhaustion);
- •Subjects deemed by the investigator to be at high risk for general/local anesthesia;
- •Pregnant or lactating women, or those with a positive β-human chorionic gonadotropin (β-HCG) test during screening, or those unable or unwilling to adopt effective non-pharmacological contraceptive measures during the study and for 6 months after study completion;
- •Other circumstances deemed by the investigator as unsuitable for participation in this trial.
研究组 & 干预措施
Dose escalation
Four different doses were set, and three subjects in each dose plan received human umbilical cord mesenchymal stem cell injection successively. Each subject received a single dose of 6.0*10^6, 3.0*10^7, 6.0*10^7, and 1.2*10^8 cells / person.
干预措施: Human umbilical cord mesenchymal stem cell injection (Drug)
结局指标
主要结局
Tolerance of patients with idiopathic fibrosis to human umbilical cord mesenchymal stem cell injection
时间窗: From the first administration to 4 weeks after administration
Incidence and severity of adverse events according to CTCAE5.0
Dose exploration of patients with idiopathic fibrosis to human umbilical cord mesenchymal stem cell injection
时间窗: From the first administration to 4 weeks after administration
The maximum tolerable dose (MTD) of a single administration depends on whether dose limiting toxicity (DLT) occurs within 4 weeks after the first administration, for example (1) Hematological toxicity of grade 3 and above caused by the treatment of human umbilical cord mesenchymal stem cell injection, （2） There are grade 3 and above non hematological toxic reactions caused by the treatment of human umbilical cord mesenchymal stem cell injection, except for the following cases, (3) Any other toxicity related to cell therapy that is higher than the baseline level is judged as clinically significant and / or unacceptable by the investigator and the sponsor, (4) There are acute exacerbations and serious adverse events (SAE) of IPF related to the treatment of human umbilical cord mesenchymal stem cell injection (which may be related, likely to be related and definitely related)
次要结局
- Preliminary efficacy evaluation(The 4th, 12th, 24th and 48th week after administration)