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Main objective: To explore the safety and tolerability of human umbilical cord mesenchymal stem cell injection in the treatment of interstitial lung disease (ILD); Secondary objective: To explore the preliminary effectiveness of human umbilical cord mesenchymal stem cell therapy for interstitial lung disease (ILD) and recommend appropriate cell therapy doses for subsequent clinical studies; Exploring the immunogenicity of human umbilical cord mesenchymal stem cell injection in the treatment of interstitial lung disease (ILD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose escalation | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Human umbilical cord mesenchymal stem cell injection | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose per dose (MTD) | 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. 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Preliminary efficacy evaluation：lung function | Changes from baseline in lung function (forced vital capacity, diffusion capacity for carbon monoxide) in the treatment of Interstitial lung disease(ILD), and to recommend the appropriate dose of cell therapy for subsequent clinical studies. Forced vital capacity(FVC) in litre(L); Diffusion capacity for carbon monoxide(DLCO) in ml/min/mmHg | The 4th, 12th, 24th week after administration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lu Gang, Vice President | Contact | 086-13701662450 | glu@shlifestemcell.com | |
| Wang Kai, Project Manager | Contact | 086-17601600819 | kwang@shlifestemcell.com |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38648021 | Background | Maher TM. Interstitial Lung Disease: A Review. JAMA. 2024 May 21;331(19):1655-1665. doi: 10.1001/jama.2024.3669. | |
| 24754826 | Background | Rosas IO, Dellaripa PF, Lederer DJ, Khanna D, Young LR, Martinez FJ. Interstitial lung disease: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases. Ann Am Thorac Soc. 2014 Apr;11 Suppl 3(Suppl 3):S169-77. doi: 10.1513/AnnalsATS.201312-429LD. |
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| ID | Term |
|---|---|
| D017563 | Lung Diseases, Interstitial |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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Dose1 Group：6.0×10^6 cells/person, single-dose Dose2 Group：3.0×10^7 cells/person, single-dose Dose3 Group：6.0×10^7 cells/person, single-dose Dose4 Group：9.0×10^7 cells/person, single-dose
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| Preliminary efficacy evaluation: St. George's respiratory questionnaire(SGRQ) | Changes from baseline in score of St. George's respiratory questionnaire(SGRQ). To study the value of St George s respiratory questionnaire(SGRQ) in evaluating the life quality of patients with ILD, and to recommend the appropriate dose of cell therapy for subsequent clinical studies. St. George's respiratory questionnaire(SGRQ) score: Range 0-100,The higher the score, the more severe the impact of the disease on symptoms, activities, and daily life. | The 4th, 12th, 24th week after administration |
| Preliminary efficacy evaluation: dyspnea score | Changes from baseline in value of dyspnea score. To study the value of dyspnea score(modified Medical Research Council, mMRC) in evaluating the life quality of patients with ILD, and to recommend the appropriate dose of cell therapy for subsequent clinical studies. Dyspnea score(mMRC)：Range 0-4,mMRC levels 0-1 indicate few symptoms, mMRC levels 2-3 indicate multiple symptoms, and level 4 indicates difficulty breathing at the slightest level of activity. | The 4th, 12th, 24th week after administration |
| Preliminary efficacy evaluation: cough score | Changes from baseline in value of cough score. To study the value of cough score(Cough Evaluation Test, CET) in evaluating the life quality of patients with ILD, and to recommend the appropriate dose of cell therapy for subsequent clinical studies. Cough score(Cough Evaluation Test, CET)：Range 5-25, the higher the score, the more severe the daytime cough, the greater the impact of nighttime cough on sleep, and the greater the impact of cough on daily life and psychology. | The 4th, 12th, 24th week after administration |
| Preliminary efficacy evaluation: 6-minute walk test | Changes from baseline in result of 6-minute walk test (grade and distance) in the treatment of Interstitial lung disease(ILD), and to recommend the appropriate dose of cell therapy for subsequent clinical studies. Draw a straight distance of 30.5 meters (100 feet) on a flat surface, and place a chair at each end as a marker. The subjects walked back and forth between them, with the pace determined by their own physical abilities. The personnel monitoring on the side report the time every 2 minutes and record any discomfort such as shortness of breath or chest pain that the subject may experience. | The 4th, 12th, 24th week after administration |
| Preliminary efficacy evaluation: Frequency of acute exacerbation events | Changes from baseline in Frequency of acute exacerbation events in the treatment of Interstitial lung disease(ILD), and to recommend the appropriate dose of cell therapy for subsequent clinical studies | The 4th, 12th, 24th week after administration |
| Preliminary efficacy evaluation: High Resolution Computed Tomography scores(HRCT score) | Changes from baseline in chest High Resolution Computed Tomography scores(Warrick score) in the treatment of Interstitial lung disease(ILD), and to recommend the appropriate dose of cell therapy for subsequent clinical studies. HRCT score(Warrick score): Range 0-30,the higher the score, the more severe the lesion type and the wider the lesion range. | The 4th, 12th, 24th week after administration |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：Blood pressure | Blood pressure in millimeter of mercury(mmHg) | The 4th, 12th, 24th week after administration |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：Pulse | Pulse in beats per minute | The 4th, 12th, 24th week after administration |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：respiration rate | Respiration rate in times/minute | The 4th, 12th, 24th week after administration |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：body temperature | Body temperature in centigrade(℃) | The 4th, 12th, 24th week after administration |
| Blood routine | White blood cell count (WBC) in 10^9/L; Neutrophil count (Neu) in 10^9/L; Lymphocyte count (Lym) in 10^9/L; Monocyte count (Mon) in 10^9/L; Eosinophil count (Eos) in 10^9/L; Basophil count(Bas) in 10^9/L; Red blood cell count (RBC) in 10^9/L; Platelets(PLT) in 10^9/L; Hemoglobin (HGB) in g/L; Mean corpuscular hemoglobin concentration (MCHC) in g/L; Hematocrit (HCT) in percentage(%); Mean corpuscular volume (MCV) in femtoliter(fL). | The 4th, 12th, 24th week after administration |
| Blood biochemistry | Total protein (TP) in g/L; Albumin (ALB) in g/L; Total bilirubin (TBIL) in umol/L, Direct bilirubin (DBIL) in umol/L, Total bile acid (TBA) in umol/L, Creatinine (Cr) in umol/L, Uric acid (UriC) in umol/L; Alanine aminotransferase (ALT) in U/L Aspartate aminotransferase (AST) in U/L; Alkaline phosphatase (ALP) in U/L; Gamma glutamyl transpeptidase (GGT) in U/L; Lactate dehydrogenase (LDH) in U/L; Fasting blood glucose (Glu) in mmol/L; Potassium ions (K+) in mmol/L; Sodium ions (Na+) in mmol/L; Chloride ions (Cl -) in mmol/L; Calcium ions (Ca2+) in mmol/L; Glycated hemoglobin (HbA1c) in percentage(%); | The 4th, 12th, 24th week after administration |
| Blood gas analysis | PH; Arterial partial pressure of oxygen (PaO2) in mmHg Arterial partial pressure of carbon dioxide (PaCO2) in mmHg | The 4th, 12th, 24th week after administration |
| Concentration of Lung tumor markers | Cytokeratin 19 fragment (CYFRA21-1) in ng/mL; Neuron specific enolase (NSE) in ng/mL; Squamous cell carcinoma antigen (SCC) in ng/mL; Carcinoembryonic antigen (CEA) in ng/mL; Carbohydrate antigen(CA125) in Unit/mL. | The 4th, 12th, 24th week after administration |
| Electrocardiogram | Heart rate in beats/minute; PR interval in millisecond(ms) QRS interval in millisecond(ms) QT interval (uncorrected) in millisecond(ms) | The 4th, 12th, 24th week after administration |
| 34853093 | Background | Gille T, Laveneziana P. Cardiopulmonary exercise testing in interstitial lung diseases and the value of ventilatory efficiency. Eur Respir Rev. 2021 Nov 30;30(162):200355. doi: 10.1183/16000617.0355-2020. Print 2021 Dec 31. |
| 21569606 | Background | Hass R, Kasper C, Bohm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 2011 May 14;9:12. doi: 10.1186/1478-811X-9-12. |
| 19497992 | Background | Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, Boyd R, Trounson A. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol. 2009 Jul;175(1):303-13. doi: 10.2353/ajpath.2009.080629. Epub 2009 Jun 4. |
| 31613055 | Background | Averyanov A, Koroleva I, Konoplyannikov M, Revkova V, Lesnyak V, Kalsin V, Danilevskaya O, Nikitin A, Sotnikova A, Kotova S, Baklaushev V. First-in-human high-cumulative-dose stem cell therapy in idiopathic pulmonary fibrosis with rapid lung function decline. Stem Cells Transl Med. 2020 Jan;9(1):6-16. doi: 10.1002/sctm.19-0037. Epub 2019 Oct 15. |
| 25039426 | Background | Chambers DC, Enever D, Ilic N, Sparks L, Whitelaw K, Ayres J, Yerkovich ST, Khalil D, Atkinson KM, Hopkins PM. A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis. Respirology. 2014 Oct;19(7):1013-8. doi: 10.1111/resp.12343. Epub 2014 Jul 9. |
| 27890713 | Background | Glassberg MK, Minkiewicz J, Toonkel RL, Simonet ES, Rubio GA, DiFede D, Shafazand S, Khan A, Pujol MV, LaRussa VF, Lancaster LH, Rosen GD, Fishman J, Mageto YN, Mendizabal A, Hare JM. Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial. Chest. 2017 May;151(5):971-981. doi: 10.1016/j.chest.2016.10.061. Epub 2016 Nov 24. |