Human Umbilical Cord Mesenchymal Stem Cell Injection for the Treatment of Interstitial Lung Disease

Official title

An Open Clinical Study Exploring the Safety, Tolerability, and Preliminary Efficacy of Human Umbilical Cord Mesenchymal Stem Cell Injection in the Treatment of Interstitial Lung Disease (ILD)

Overview

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).

Interventions

• Drug Human umbilical cord mesenchymal stem cell injection
  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.

Primary outcome measures

• Maximum tolerated dose per dose (MTD) [Time frame: From the first administration to 4 weeks after administration]

Secondary outcome measures (12)

• Preliminary efficacy evaluation：lung function [Time frame: The 4th, 12th, 24th week after administration]
• Preliminary efficacy evaluation: St. George's respiratory questionnaire(SGRQ) [Time frame: The 4th, 12th, 24th week after administration]
• Preliminary efficacy evaluation: dyspnea score [Time frame: The 4th, 12th, 24th week after administration]
• Preliminary efficacy evaluation: cough score [Time frame: The 4th, 12th, 24th week after administration]
• Preliminary efficacy evaluation: 6-minute walk test [Time frame: The 4th, 12th, 24th week after administration]
• Preliminary efficacy evaluation: Frequency of acute exacerbation events [Time frame: The 4th, 12th, 24th week after administration]
• Preliminary efficacy evaluation: High Resolution Computed Tomography scores(HRCT score) [Time frame: The 4th, 12th, 24th week after administration]
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：Blood pressure [Time frame: The 4th, 12th, 24th week after administration]
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：Pulse [Time frame: The 4th, 12th, 24th week after administration]
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：respiration rate [Time frame: The 4th, 12th, 24th week after administration]
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：body temperature [Time frame: The 4th, 12th, 24th week after administration]
• Blood routine [Time frame: The 4th, 12th, 24th week after administration]

Eligibility criteria

Inclusion criteria

• Gender not limited, age ≥ 18 years old (including threshold);
• Clinical diagnosis of interstitial lung disease;
• Blood biochemistry tests must meet the following criteria: alanine aminotransferase (ALT) ≤ 2.5 × ULN, aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin (TBIL) ≤ 2 × ULN, direct bilirubin (DBIL) ≤ 1.5 × ULN, or creatinine (Cr) ≤ 3 × ULN;
• The diffusion capacity of carbon monoxide (DLCO) (corrected by Hb) in lung function tests within the previous 3 months is 30% to 80% of the expected value (including 30% and 80%); Forced vital capacity (FVC) is 40% to 70% of the estimated value (including 40% and 70%)

Exclusion criteria

• Within the first 3 days of enrollment, use high-dose corticosteroids (equivalent to methylprednisolone>240 mg/day) or irregularly use systemic corticosteroids;
• For patients receiving immunosuppressive therapy, unstable background treatment with cyclophosphamide, mycophenolate mofetil/sodium, methotrexate, or other immunosuppressive monotherapy is not allowed (combination therapy is not allowed)
• Diagnose IPF patients who have previously taken drugs that may cause or worsen pulmonary fibrosis;
• Individuals with a history of mechanical ventilation or concurrent infectious pneumonia or asthma within the previous month prior to screening; Patients with airway obstruction disease (FEV1/FVC<0.7 before using bronchodilators); Patients with other clinically significant serious abnormalities in the lungs; Currently requiring oxygen therapy treatment (oxygen therapy time>15h/d);
• Pregnant and lactating women
• Screening for malignant tumors that have occurred within the past 5 years, excluding cervical carcinoma in situ, squamous cell carcinoma of the skin, or basal cell carcinoma that have been previously treated for curative purposes;
• Individuals who have been hospitalized for 3 or more times due to acute exacerbation of ILD or other respiratory diseases within the past year prior to screening
• There is evidence that subjects currently have digestive system, urinary system, cardio cerebrovascular, blood system, nervous system, mental and metabolic diseases that may affect safety, such as type 2 diabetes with poor blood sugar control, hypertension with poor blood pressure control, etc
• have a history of abuse or drug use of psychotropic substances
• individuals allergic to human serum albumin, anesthetics, or their components
• Select participants who have participated in any other clinical trials within the previous 3 months;
• individuals who have previously received stem cell therapy
• Researchers have determined that the expected survival period may be less than 1 year;
• Subjects who cannot tolerate bronchoscopy examination (including but not limited to: active massive hemoptysis; severe hypertension and arrhythmia;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Maher TM. Interstitial Lung Disease: A Review. JAMA. 2024 May 21;331(19):1655-1665. doi: 10.1001/jama.2024.3669. PMID 38648021
• 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. PMID 24754826
• 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. PMID 34853093
• 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. PMID 21569606
• 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. PMID 19497992
• 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. PMID 31613055
• 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. PMID 25039426
• 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. PMID 27890713

Identifiers

NCT: NCT06534528 · SHLF-MSC-ILD-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗