Clinical trial NCT05468502: Phase I/IIa Clinical Trial of Human Umbilical Cord Mesenchymal Stem Cell Injection in the Treatment of Idiopathic Pulmonary Fibrosis (IPF)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Idiopathic pulmonary fibrosis
IPF
Lead sponsor: Shanghai Life Science & Technology
Sponsor class: INDUSTRY
First posted: 2022-07-21
Enrollment: 18
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Tolerance of patients with idiopathic fibrosis to human umbilical cord mesenchymal stem cell injection
timeFrame: From the first administration to 4 weeks after administration
measure: Dose exploration of patients with idiopathic fibrosis to human umbilical cord mesenchymal stem cell injection
timeFrame: From the first administration to 4 weeks after administration
Secondary outcomes:
measure: Preliminary efficacy evaluation
timeFrame: The 4th, 12th, 24th and 48th week after administration
measure: Preliminary efficacy evaluation
timeFrame: The 4th, 12th, 24th and 48th week after administration
Other outcomes:
measure: Preliminary efficacy evaluation
timeFrame: The 4th, 12th, 24th and 48th week after administration
measure: Preliminary efficacy evaluation
timeFrame: The 12th, 24th and 48th week after administration
measure: Preliminary efficacy evaluation
timeFrame: The 12th, 24th and 48th week after administration
measure: Preliminary efficacy evaluation
timeFrame: Within 48 weeks after administration
measure: Immunogenicity of human umbilical cord mesenchymal stem cells
timeFrame: The 1st and 4th weeks after administration
measure: Immunogenicity of human umbilical cord mesenchymal stem cells
timeFrame: The 1st and 4th weeks after administration
Locations:
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
Study officials:
References:
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citation: 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.
citation: Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schunemann HJ; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824. doi: 10.1164/rccm.2009-040GL.