Phase I/IIa Clinical Trial of Human Umbilical Cord Mesenchymal Stem Cell Injection in the Treatment of Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Human umbilical cord mesenchymal stem cell injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) Age 50 75 years old (including the threshold), regardless of gender; (2) IPF was diagnosed according to the diagnostic guidelines for idiopathic pulmonary fibrosis jointly issued by the American Thoracic Society (ATS), the European Respiratory Society (ERs), the Japanese Respiratory Society (JRS) and the Latin American Thoracic Association (ALAT) in 2018; (3) Subjects with typical imaging manifestations of IPF (honeycomb, stretch bronchiectasis or bronchiectasis (mainly in ground glass shadow and fine mesh shadow) on HRCT within 12 months before screening; (4) Within 3 months before administration, the researcher determined that the disease was stable. The pulmonary carbon monoxide diffusion volume (DLCO) was 30% - 79% of the predicted value (corrected by HB value), or FVC was 50% - 80% of the predicted value; (5) Blood biochemical examination should meet the following standards: alanine aminotransferase (ALT) ≤ 1.5uln, aspartate aminotransferase (AST) ≤ 1.5uln, total bilirubin (TBIL) ≤ 1.5uln, direct bilirubin (DBIL) ≤ 1.5uln, blood creatinine (CR) ≤ 1.5uln; (6) Expected survival ≥ 12 months; (7) Subjects who have good compliance, can understand and cooperate with the completion of pulmonary function examination, are willing to take drugs according to the requirements of the protocol and receive follow-up examination on time; (8) Subjects who voluntarily participated in the trial, understood and signed the informed consent form. Exclusion Criteria: (1) Have previously received stem cell therapy, or are intolerant to cell therapy, or have taken drugs that may cause or aggravate pulmonary fibrosis (such as amiodarone, bleomycin or methotrexate); (2) Suffering from interstitial lung disease (ILD) other than IPF, including but not limited to: any other type of interstitial pneumonia; Lung disease related to exposure to fibroblasts or other environmental toxins or drugs; Other types of occupational lung disease; Granulomatous pulmonary disease; Pulmonary vascular disease; Systemic diseases, including vasculitis, infectious diseases (i.e. tuberculosis) and connective tissue diseases; (3) Those who need oxygen therapy at present (oxygen therapy time 15h/d); (4) Those who used or planned to use nidanib during the study 1 month before screening; (5) Subjects with a history of mechanical ventilation or complicated with infectious pneumonia and asthma within 1 month before screening; (6) Patients with malignant tumors within 5 years before screening; (7) Those who have been hospitalized for 3 times or more due to acute exacerbation of IPF or other respiratory diseases within 1 year before screening; (8) There is evidence that the subjects currently have digestive, urinary, cardiovascular, cerebrovascular, hematological, nervous, mental and metabolic diseases that may affect safety, such as type 2 diabetes with poor blood glucose control (fasting blood glucose ≥ 10.0mmol/l or HbA1c ≥ 8.0%), hypertension with poor blood pressure control (≥ 160/100mmhg), etc; (9) Have a history of psychotropic drug abuse and drug abuse; (10) People with known history of immune system (such as thymus disease and systemic lupus erythematosus); (11) Patients with positive serum Virology (HBsAg, HCV antibody, HIV antibody, Treponema pallidum antibody), including hepatitis B virus carriers, patients with stable hepatitis B after drug treatment (DNA titer ≤ 500iu/ml or copy number < 1000copies/ml) and cured patients with hepatitis C (HCV RNA test negative) can be enrolled after being judged to be qualified by the researcher; (12) People who are allergic to human albumin, narcotic drugs or their ingredients; (13) Subjects who participated in any other clinical trials within the first 3 months of screening; (14) Subjects who cannot tolerate bronchoscopy (including but not limited to the following conditions: active massive hemoptysis; severe hypertension and arrhythmia; myocardial infarction or history of unstable angina pectoris within 4-6 weeks before screening; severe cardiopulmonary dysfunction; uncorrectable bleeding tendency (platelet count < 60 × 109/l), such as severe coagulation dysfunction, uremia and severe pulmonary hypertension; Severe superior vena cava obstruction syndrome; Suspected aortic aneurysm; Multiple pulmonary bullae; General condition (extreme failure); (15) The researchers judged that the risk of general anesthesia / local anesthesia was higher; (16) Human chorionic gonadotrophin in pregnancy or lactation, or screening β （ β- HCG) positive, or unable and unwilling to take effective non drug contraceptives during the study period and 6 months after the end of the study; (17) Other circumstances that the researcher believes are not suitable for entering this test.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>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 9.0*10^7 cells / person. | Drug: Human umbilical cord mesenchymal stem cell injection<br>* Different doses of human umbilical cord mesenchymal stem cell injection were infused to the focus of patients with idiopathic pulmonary fibrosis through bronchoscope, and the tolerance of subjects to different doses of human umbilical cord mesenchymal stem cell injection was observed, and the curative effect was preliminarily observed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance of patients with idiopathic fibrosis to human umbilical cord mesenchymal stem cell injection | Incidence and severity of adverse events according to CTCAE5.0 | From the first administration to 4 weeks after administration | 
| Dose exploration of patients with idiopathic fibrosis to human umbilical cord mesenchymal stem cell injection | 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) | From the first administration to 4 weeks after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary efficacy evaluation | Changes from baseline in St. George's respiratory questionnaire SGRQ, dyspnea score, cough score and 6-minute walk test (grade and distance)in the treatment of idiopathic pulmonary fibrosis (IPF), and to recommend the appropriate dose of cell therapy for subsequent clinical studies | The 4th, 12th, 24th and 48th week after administration | 
| Preliminary efficacy evaluation | Changes in lung function (FVC, DLCO sb) compared with baseline | The 4th, 12th, 24th and 48th week after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic pulmonary fibrosis, IPF